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IN    SURGICAL  AND 
GENERAL  PRACTICE 


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Fiontispiece 


THE    NEW    PHYSIOLOGY 

IN    SURGICAL 
AND   GENERAL   PRACTICE 


By  a.  RENDLE   SHORT, 

M.D.,  B.S.,  B.Sc.  (Lond.),    F.R.C.S.  CEng.), 

Examiner  in  Physiology  Jor  the  F.R.C.S.  ;    late  Hunterian  Professor,  Royal 

College  of  Surgeons ;   Senior  Assistant  Surgeon,  Bristol  Royal  Injirntarv ; 

Lecturer  on  Physiology,  University  of  Bristol. 


Fourth   Edition 
Revised  and  Enlarged 


NEW     YORK 

WILLIAM     WOOD     AND     COMPANY 
MDCCCCXX 


o^ 


"2-  0  -  3  ?  V  V 


First  Edition,  September,  igil. 

Second  Edition,    Rez'ised,    May,    IQI2. 

Reprinted,  December,  iqj2. 

Third  Edition,   June,   igi4. 

Reprinted,  July,  igib. 

Fourth  Edition,  March,  IQ20. 


^'OTE    0^     FRONTISPIECE. 

The  picture,  for  which  I  am  indebted  to  Miss  D.  PiHers  and 
Mr.  A.  K.  Maxwell,  shows  the  condition  in  the  patient  referred 
to  on  page  115. 

The  csecum  has  prolapsed  through  the  wound  in  the  abdominal 
wall,  and  is  turned  inside  out  to  show  the  mucosa.  Beneath  the 
thin  wall  of  the  caecum,  the  colls  of  small  intestine  are  seen  bulging, 
in  incessant  peristalsis. 

The  rough  sketch  at  the  top  shows  the  position  of  the  swelling 
on  the  abdominal  wall. 

In  the  upper  coloured  picture  the  sphincter  is  quiescent,  be- 
tween meals.     Notice  the  contracted  raised  muscular  ring. 

The  lower  picture  shows  the  sphincter  lying  relaxed,  and  one 
of  the  intermittent  gushes  of  fluid  ileal  contents  pouring  through, 
ten  minutes  after  a  meal. 


PREFACE    TO     FOURTH    EDITION 

The  last  edition  was  published  just  before  the  war. 
Needless  to  say  we  have  learned  a  great  deal  in  the 
past  live  years.  Research  in  pure  physiology  and 
its  applications  to  the  clinical  sciences  has  fallen 
principally  into  the  hands  of  the  Americans,  whilst 
the  British  investigators  have  devoted  themselves 
especially  to  problems  arising  out  of  the  material 
presented  by  the  wounded  in  the  war.  The  results 
of  study,  observation,  and  experiment  along  both 
these  lines  are  here  gathered  together.  Much  of 
the  book  is  new,  but  the  objects  and  scope  remain 
as  in  the  preface  to  the  original  edition.  To  make 
way  for  additional  material  considerable  sections 
have  been  deleted  altogether. 

The  chapters  on  food  deficiency  diseases,  the 
blood  and  spleen,  surgical  shock,  the  spinal  cord, 
and  the  functions  of  the  cortex,  have  been  re-written 
almost  in  their  entirety.  A  new  chapter  on  the 
heart  has  been  contributed  by  my  colleagues  Dr. 
Carey  Coombs  and  Dr.  C.  E.  K.  Herapath,  to  whom 
I  am  greatly  indebted  for  this  service.  There  are 
considerable  additions  to  the  chapter  on  digestion, 
and  less  important  changes  in  nearly  all  the  other 
parts  of  the  book.  Very  little  is  left  of  the  first 
edition,  published  in  1911. 

A.  R.  S. 

February,   1920. 


PREFACE    TO    FIRST    EDITION 

These  chapters  are  intended  for  the  general  practi- 
tioner, the  consulting  surgeon,  and  candidates  for 
the  higher  examinations  in  physiology. 

There  was  a  time  when  one  man  could  be  physio- 
logist and  surgeon  too,  but  the  rapid  march  of 
progress  in  each  field  has  left  a  great  gap  between 
the  sciences,  which  is  continually  widening.  The 
triumphs  of  the  surgeon  are  unknown  to  the  physio- 
logist, and  the  converse  is  equally  true.  Yet  many 
of  the  discoveries  of  the  past  ten  years  which  have  so 
changed  the  face  of  physiology  are  fraught  with  vast 
possibilities  for  the  clinician.  This  book  is  an  attempt 
to  sift  out  from  the  New  Physiology  that  which  is 
likely  to  be  of  value  in  the  actual  diagnosis  and 
treatment  of  patients. 

It  would  be  a  small  service  to  lay  before  the 
practical  reader  mere  theories  or  guess-work.  With 
but  few  exceptions,  only  the  estabhshed  and  settled 
conclusions  arrived  at  by  many  competent  and 
independent  workers  have  been  introduced.  Part 
of  the  chapter  on  cutaneous  anaesthetics,  and  a  few 
other  researches  and  passing  suggestions  for  which 
the  author  is  personally  responsible,  must  stand  in 
a  different  category. 


viii  PREFACE 

An  effort  has  been  made  to  explain  matters  so 
simply  that  they  may  be  intelligible  to  those  having 
the  most  elementary  knowledge  of  physiology,  and 
all  technical  terms  have  been  avoided  or  defined. 

There  are  excellent  manuals  now  published 
treating  of  the  application  of  physiology  to  diseases 
which  concern  principally  the  consulting  physician. 
This  little  book  limits  itself  to  surgical  problems,  and 
to  the  common  every-day  aspects  of  disease  that 
confront  us  all,  physicians,  surgeons,  and  general 
practitioners  ahke. 

I  owe  a  debt  of  thanks  to  my  chief.  Professor 
A.  F.  Stanley  Kent,  for  some  valuable  suggestions 
and  criticisms. 

A.  R.  S. 
Bristol, 

September,   191 1. 


CONTENTS 


I. — Food  Deficiency  Diseases    .  .  .  i 

Carboh3^drate,  protein,  and  fat  deficiences 
— Neuritis — Growth — Scurvy — Rickets. 

II. — Researches  on  Blood-  -  i6 

Recovery  of  blood  after  haemorrhage — Blood 
transfusion — The  four  blood  groups — Fate  of 
red  blood-corpuscles — Functions  of  the  spleen 
and  liver — Coagulation  of  the  blood — Purpura 
haemorrhagica  —  Haemophilia  —  Anaphylaxis — 
The  therapeutics  of  calcium  salts. 

III. — The  Heart  (by  Dr.  Carey  F.  Coombs  and  Dr. 

C.  E.  K.  Herapath)     -  -  -  -         45 

Development  and  structure  of  the  heart — 
Modes  of  examination  of  the  heart — Heart 
rhythm — Properties  of  cardiac  muscle — The 
nervous  system  of  the  heart — Cardiac  irregu- 
larities. 

IV. — Surgical  Shock  -  -  -  -  -        80 

What  is  shock  ? — The  phenomena  of  shock 
— Experimental  means  of  inducing  shock-like 
conditions — Theories  as  to  its  nature — Pre- 
vention and  treatment — Intravenous  saline 
transfusion. 

V. — Recent  Work  on    the    Functions  of    the 

Stomach  and  Intestines      -  -  .       107 

Movements  of  the  stomach — Movements  of 
the  intestine — Sensation  in  the  alimentary 
canal — Variations  in  the  hydrochloric  acid 
of  the  stomach — The  physiology  of  gastro- 
jejunostomy— Absorption  in  the  colon.   , 


X  COXTENTS 

CHAPTER  PAGE 

VI. — The  Genital  Glands    -  -  -  -        I37 

Functions  of  the  ovary — Functions  of  the 
testis — Control  of  the  genital  glands  by  internal 
secretions — The  secretion  of  milk — The  ovum 
Chemical  diagnosis  of  pregnancy. 

VII. — The  Growth  of  Bone  -  -  -       152 

Recent  change  in  our  conception  of  the  gro\vth 
of  bone — Osteoblasts — Increase  in  the  length 
of  bone — Increase  in  the  girth  of  bone — Func- 
tion of  the  periosteum — The  regenerative 
powers  of  bone — Application  of  modern  re- 
searches to  surgical  practice — Bone-grafting 
— Relation  of  the'ductless  glands  to  the  growth 
of  bone. 

VIII. — The  Thyroid  and  Parathyroid  Glands       -     166 

Histon,' — Removal  of  the  thyroid  and  para- 
thvroids-^Removal  of  the  parathyroids  alone 
— Removal  of  the  thyroid  alone — Thyroid 
feeding  —  Chemistn,'  of  thyroid  colloid  — 
Parenclwmatous  goitre — Iodoform  and  thy- 
roidism— Action  of  iodides  on  gummata  and 
atheroma  —  Exophthalmic  goitre  —  Practical 
deductions. 

IX. — The  Pituitary  and  Pineal  Glands  -       186 

Structure  of  the  Pituitary — The  effects  of 
removal  in  animals — Injection  of  extracts — 
Pituitary-  feeding — Acromegaly  and  gigantism 
• — Frohli'ch's  t^-pe — Functions  of  the  pituitan.^ 
gland — Therap'eutic  value  of  pituitary  extract 
— The  pineal  gland. 

X. — Oxaluria  -  -  -  -  -       198 


XI. — Immediate     and     Remote     Poisoning     by 

Chloroform      -     -     -     - 

Sudden  death  under  chloroform — The  fatal 

adrenalin-chloroform     combination  —  Delayed 

chloroform  poisoning. 


201 


CONTENTS  xi 

CHAPTER  TAGE 

XII. — The   Functions   of    the    Spinal  Cord   and 

Peripheral  Nerves  -  -  -       208 

The  double  motor  path — The  double  sensory- 
path — The  exact  diagnosis  of  spinal  cord  in- 
juries— Lesions  of  the  posterior  nerve  roots — 
Injuries  and  repair  of  peripheral  nerves. 

XTII. — Localization  of  Function  in  the  Brain  -       237 

Localization  of  sensation  in  the  cerebral 
cortex  ;  vision,  hearing,  cutaneous  and  other 
forms  of  sensation — Functions  of  the  frontal 
cortex  — Apraxia  — Aphasia  —  Misleading  local- 
izing signs  of  intracranial  tumour — Optic 
neuritis  —  The  cerebellum — Tumours  in  the 
cerebello-pontine  angle  —  The  cerebrospinal 
fluid. 

XIV. — The  Action  of  Cutaneous  Anesthetics  •       267 
Drugs  applied  to  the  unbroken  skin. 

Appendix  -  -  -  -  -  -      273 

Absorption  of  nitrogen  from  amino-acids. 


The  New  Physiology  in 
Snroical  and  General  Practice, 


CHAPTER    I. 
FOOD     DEFICIENCY     DISEASES. 

CARBOHYDRATE,    PROTEIN,    AND    FAT  DEFICIENCIES NEURITIS 

GROWTH — SCURVY RICKETS. 

THIS  chapter  is  not  a  discourse  on  the  phenomena 
of  starvation.  It  rather  aims  at  setting  forth 
the  consequences  that  may  be  expected  when  some 
one  more  or  less  essential  ingredient  of  the  food  is 
omitted  from  the  dietary. 

In  the  Report  of  a  Committee  of  the  Royal  Society 
on  the  "  Food  Requirements  of  Man",  issued  in 
1919,  it  is  observed  that  as  a  general  rule  the  brain 
worker  requires  from  2200  to  2600  calories  as  the 
energy  value  in  heat  units  of  his  daily  food,  whereas 
the  labourer  needs  3300  ;  but  in  the  case  of  the 
brain  worker  the  food  will  need  to  be  lighter,  more 
digestible,  and  to  contain  more  protein,  so  that  it 
will  cost  more  in  proportion. 

There  is  not  much  that  is  new  to  be  related 
concerning  the  ill-effects  of  carbohydrate  starvation. 
Except  as  a  therapeutic  measure,  it  seldom  occurs. 

1 


2  FOOD    DEFICIENCY    DISEASES 

It  leads  to  loss  of  flesh,  as  in  the  well-known  systems 
of  dieting  for  obesity,  and  to  an  increase  in  the 
formation  of  /3-oxybutyric  and  diacetic  acids  in  the 
blood. 

Chittenden's  work  at  Yale  University  showed  that 
it  is  possible  to  maintain  life,  and  apparently  both 
mental  and  physical  efficiency,  on  a  diet  containing 
less  than  half  the  amount  of  protein  allowed  in  the 
standard  dietaries.  Hindhede,  of  Copenhagen,  by 
supplying  an  ample  total  calorie  value  of  food  (4000 
calories  per  day) ,  was  able  to  maintain  his  laboratory 
attendant  in  health  for  150  days  on  a  diet  of  nothing 
but  potatoes,  margarine,  and  onions,  containing  only 
4-425  grms.  of  nitrogen  a  day.  It  is  very  doubtful, 
however,  whether  the  results  would  be  satisfactory 
over  a  longer  time.  It  has  been  demonstrated  that 
the  mental  and  physical  efficiency  of  the  various  races 
of  India,  many  of  whom  live  very  near  the  protein- 
starvation  level,  varies  directly  with  the  protein 
allowance  in  their  dietary.  The  Royal  Society 
Committee  report  that  the  diet  of  the  average  man 
should  contain  not  less  than  70  to  80  grms.  of 
protein  daily,  and  that  some  of  it  should  be  of 
animal  origin. 

A  colossal  experiment  in  fat-starvation  has  been 
carried  out  on  the  population  of  Germany  and  the 
other  Central  European  states.  So  far  the  informa- 
tion which  has  come  through  is  too  scanty  to  build 
much  upon.  We  have  heard  of  a  high  infantile 
mortality,  of  general  loss  of  flesh,  of  bodily  and 
mental  torpor,  of  increased  liability  to  tuberculosis, 
and  so  on.     As  might  be  expected,  it  is  reported  (by 


FOOD    DEFICIENCY    DISEASES  3 

medical  members  of  a  commission  of  the  Society  of 
Friends)  that  rickets  has  become  a  widespread 
scourge  amongst  German  infants.  The  only  new 
fat-deficiency  disease  I  have  been  able  to  get  any 
account  of  is  a  chronic  affection  of  the  conjunctivae 
in  infants  (xerophthalmia)  reported  from  Denmark 
and  elsewhere.  There  seems  to  be  a  close  relation 
between  the  assimilation  of  fat  and  the  capacity 
for  bodily  work.  "  Where  vigorous  muscular 
exercise  has  to  be  undertaken,  it  is  essential  that 
the  diet  should  contain  not  less  than  25  per  cent 
of  its  energy  in  the  form  of  fat ". 

NEURITIS. 

For  generations  it  has  been  a  fundamental  axiom 
of  dietetics  that  a  proper  food  allowance  should 
contain  proteins,  carbohydrates,  fats,  salts,  and 
water.  Tables,  such  as  Ranke's,  have  been  drawn 
up  and  copied  from  book  to  book,  setting  forth  the 
proper  proportions  of  each  to  maintain  health. 
During  the  past  six  or  seven  years,  however,  im- 
portant evidence  has  been  adduced  to  show  that 
these  five  proximate  principles  by  themselves  are 
inadequate,  and  that  a  mysterious  something  more 
is  necessary. 

One  of  the  first  reforms  leading  up  to  the  marvellous 
emancipation  of  modern  Japan  from  her  mediaevalism 
of  half  a  century  ago  was  concerned  with  a  problem 
of  this  sort.  The  Japanese  navy  was  reduced  to 
complete  ineptitude  by  the  prevalence  of  beri-beri — 
a  form  of  peripheral  neuritis — amongst  the  crews,  as 
many  as  a  quarter  of  the  men  being  afflicted.     Baron 


4  FOOD    DEFICIENCY    DISEASES 

Takaki,  lately  returned  to  his  own  country  after  a 
study  of  modern  medicine,  found  that  the  dietary 
was  very  imperfect,  and  instituted  an  improved 
ration  with  complete  success.  Beri-beri  was  until 
recently  a  terrible  scourge  amongst  the  inhabitants 
of  the  Malay  States  ;  was  often  seen  in  coolies  at 
English  seaports  ;  and  has  broken  out  in  an  asylum 
in  Dublin.  Improving  the  quantity  of  food  in  the 
prisons  of  the  Straits  Settlements  failed  to  limit  the 
disease. 

The  outstanding  feature  of  the  incidence  of  beri- 
beri in  the  Straits  was,  that  while  the  Tamils  were 
exempt,  the  Chinese  suffered  severely.  Rice  is  the 
main  article  of  diet  with  both  races,  but  with  this 
difference,  that  whereas  the  Tamils  store  their  rice 
and  boil  it  in  husk,  the  Chinese  use  husked  white 
rice  such  as  we  are  accustomed  to  in  this  country, 
though,  of  course,  with  us  rice  is  a  very  much  less 
important  item  in  the  daily  dietary.  The  Chinese 
are  extremely  prone  to  beri-beri ;  the  Tamils  very 
seldom  suffer.  This  cannot  be  due  to  any  racial 
peculiarity,  because  Tamils  in  prison  and  fed  on 
husked  rice  are  just  as  liable  as  the  Chinese. 

The  explanation  originally  given  was  that  the 
bare  rice  grain  had  become  contaminated  in  some 
way  ;  but  recent  experiments  by  Casimir  Funk  and 
others  bring  out  another  aspect  of  the  case.  It  is 
possible  in  pigeons  to  produce  a  peripheral  neuritis 
closely  resembling  beri-beri  by  feeding  exclusively 
on  polished  rice,  and  when  small  quantities  of  husk 
are  added  the  birds  rapidly  recover.  The  essential 
constituent  of  the  husk  which  has  this  effect  is  only 


FOOD     DEFICIENCY    DISEASES  5 

present  in  small  quantity,  but  it  can  be  isolated  in 
crystalline  form,  and  on  analysis  appears  to  belong 
to  the  pyrimidine  group.  It  is  not  the  coarse 
fibrous  husk  that  contains  so  much  of  the  anti- 
neuritic  substance,  but  the  thin  film  or  '  silver  skin ' 
just  covering  the  grain,  wherein  also  lies  the  embryo. 
Wheat  embryo,  wheat  bran,  yeast,  and  egg  yolk 
also  contain  fair  quantities  of  this  element ;  milk 
and  meat  only  hold  traces.  From  loo  kilos  of  yeast 
2*5  grms.  of  the  crystals  were  obtained. 

There  is  clinical  evidence  in  support  of  this  experi- 
mental work.  Research  in  the  Philippines  has  shown 
that  the  infant  of  a  mother  fed  on  polished  rice  is 
Hkely  to  develop  beri-beri,  but  that  it  is  rapidly  cured 
either  by  fresh  cow's  milk  or  by  an  extract  of  rice- 
husk.  The  substitution  of  parboiled  for  polished 
rice  in  a  Siam  prison  has  brought  down  the  death- 
rate  from  113  to  nil. 

McCarrison  shows  that  it  is  not  only  the  nerves 
that  are  affected  by  a  diet  restricted  to  polished 
rice.  The  thymus,  testes,  ovaries,  and  spleen  all 
atrophy,  and  in  a  less  degree  the  pancreas,  heart, 
liver,  and  kidney.  The  suprarenals,  on  the  other 
hand,  become  hypertrophied,  and  there  is  usually 
oedema,  which  seems  to  run  parallel  to  the  degree  of 
enlargement  of  the  suprarenals.  Doubtless  this 
accounts  for  the  '  wet '  form  of  beri-beri,  and 
perhaps  for  '  war  oedema '  amongst  prisoners  in 
Germany. 

GROWTH. 

The  principle  having  been  once  established  that  a 
dietary  to  maintain  health  must  contain,  in  addition 


6  FOOD    DEFICIENCY    DISEASES 

to  the  five  well-known  elements — proteins,  carbo- 
hydrates, fats,  salts,  and  water — traces  of  other  so- 
far  unrecognized  chemicals,  a  new  field  is  opened 
for  exploration,  and  several  diseases  come  up  for  a 
similar  explanation.  The  new  chemical  bodies  which 
appear  to  be  thus  needful  are  called  '  vitamines  '. 

Hopkins  has  lately  shown  that  something  of  the 
sort  is  necessary  for  ordinary  growth.  Young  rats 
fed  on  purified  protein,  carbohydrate,  fat,  salts,  and 
water,  absolutely  cease  to  grow,  even  if  the  quantity 
supplied  is  correct.  If  the  experiment  is  prolonged, 
the  animals  die.  If  only  a  teaspoonful  of  milk  is 
supplied  daily,  growth  becomes  normal.  We  now 
know  that  two  vitamines  are  necessary  for  growth  ; 
one  of  these  is  called  fat-soluble  A,  and  is  contained 
dissolved  in  the  fat  of  milk,  and  the  other  is  water- 
soluble  B,  which  appears  to  be  identical  with  the 
antineuritic  vit amine.  Considerable  research  has 
been  done  lately  on  the  fat-soluble  A.  It  is  shown 
by  Halliburton  and  Drummond,  using  young  rats, 
that  none  of  the  vegetable  margarines  which  have 
come  into  such  extensive  use  of  late  contain  it.  It  is 
present  in  milk,  butter,  cream,  animal  fat,  and  the 
higher-priced  (oleo-oil)  beef-fat  margarines.  Lard 
contains  little  if  any  ;  it  has  been  spoiled  in  the 
process  of  preparation.  The  fat-soluble  vitamine  in 
mother's  milk  is  derived  in  considerable  part  from 
cow's  milk  or  cream  she  has  taken  as  nourishment. 
These  observations  go  to  show  the  national  impor- 
tance of  providing  milk  and  animal-derived  fats 
both  for  young  children  and  also  for  nursing 
mothers. 


FOOD     DEFICIENCY     DISEASES  7 

Even  sarcoma-cells  require  vitamines,  and  if  they 
are  withheld,  Jensen's  rat  sarcoma  only  develops  at 
a  quarter  its  usual  rate.  At  Romney  there  are  two 
fields,  apparently  identical,  but  the  animals  pasturing 
in  the  one  put  on  flesh,  and  in  the  other  they  become 
thin. 

SCURVY. 

It  has  been  known  for  centuries  that  scurvy  is  a 
deficiency  disease  ;  but  exactly  where  the  deficiency 
lies  has  always  been  uncertain.  Nowadays  it  is  very 
rare  in  adults  in  this  country,  though  the  writer 
has  seen  one  case  affecting  a  lonely  man  who  was 
trying  to  live  on  his  old-age  pension.  A  few  cases 
occurred  in  France  during  the  war.  I  saw  one  quite 
severe  example  of  the  disease  at  a  casualty  clearing 
station.  The  man  had  been  a  long  time  in  the 
trenches,  and  had  had  no  fresh  food. 

Much  more  commonly  the  disease  is  seen  in  young 
infants  fed  upon  boiled,  stale,  or  artificially-prepared 
milk. 

Some  most  interesting  and  important  points  have 
lately  come  to  light  with  regard  to  scurvy.  It  should 
be  remembered  that  the  swollen  gums,  loose  teeth, 
haemorrhages  from  the  mucous  membranes  and 
beneath  the  skin  and  periosteum,  and  grave  anaemia, 
are  signs  of  an  advanced  degree  of  the  food  deficiency. 
There  are  less  characteristic  symptoms  long  before 
these  develop — lassitude,  inability  to  think  or  work, 
and  general  debility.  When  these  signs  appear  in 
a  body  of  men,  undeclared  scurvy  should  be  thought 
of. 

It  has  been  an  article  of  faith  for  nearly  a  century 


8  FOOD    DEFICIENCY    DISEASES 

that  lime-  or  lemon-juice,  and  fresh  vegetables,  are 
the  main  preventives  of  scurvy,  and  yet  there  have 
been  curious  gaps  in  the  evidence.  Up  to  the 
beginning  of  the  eighteenth  century,  both  the  British 
Navy  and  the  mercantile  service  had  suffered  terribly 
from  the  disease,  and  many  expeditions  were  ruined 
in  consequence.  In  the  days  of  Robinson  Crusoe 
the  antiscorbutic  properties  of  lemons  and  fresh  fruit 
and  vegetables  were  known,  but  the  supineness  of 
the  authorities  was  such  that  often  no  trouble  was 
taken  to  provide  sailors  with  them  until  about  1803, 
when  the  Navy  began  to  get  a  regular  supply  of 
lemon-juice  from  Malta.  It  was  often  caUed  '  lime- 
juice  '.  After  about  1865  the  juice  of  Montserrat 
limes  came  to  be  used  instead,  and  this  has  been  the 
main  standby  in  the  Army  and  Navy  ever  since. 
From  1803  onwards  there  has  been  very  little 
scur\'y.  The  use  of  fruit- juices  became  compulsory 
in  the  merchant  service  after  1844,  and  was  equally 
successful.  Of  course,  shorter  voyages  and  better 
food  supplies  generally  have  led  to  less  and  less  need 
to  place  rehance  on  lime-  or  lemon-juice  under 
ordinary  circumstances.  In  several  Arctic  expedi- 
tions, such  as  Sir  James  Ross's  in  1849,  the  lemon- 
juice  supplied  was  thoroughly  bad,  and  the  company 
suffered  severely  from  scurvy.  Thus  far  the  evidence 
is  clear.  There  have  been,  however,  several  occasions 
when  no  fresh  vegetables  and  no  fruit-juice  have 
been  used  for  long  periods,  but  fresh  meat  in  large 
quantity  has  been  eaten,  and  no  scurvy  has  occurred. 
This  was  so  with  Nansen's  expedition  across  Green- 
land,   and   with    one   of   the    subsidiary   parties   in 


FOOD     DEFICIENCY     DISEASES  9 

Shackleton's  expedition  to  the  South  Pole.  The 
Hudson's  Bay  Company  people  Uve  almost  entirely 
on  fresh  meat  and  fish,  and  they  never  show  signs 
of  the  disease.  Yet  fresh  meat  has  failed  to  avert 
scurvy  (as  in  the  Kaffir  campaign  of  1846-7)  when 
plenty  of  other  food  is  taken  at  the  same  time. 
Evidently  the  amount  of  vitamine  in  fresh  meat 
is  low,  and  unless  it  is  eaten  in  great  quantity  it 
proves  inadequate.  Also,  the  traditional  Army 
stew  probably  destroys  much  of  the  vitamine  by 
long  cooking. 

During  the  war,  doubts  have  grown  up  as  to  the 
preventive  value  of  lime-juice.  This  has  led  Miss 
Alice  Henderson  Smith  to  bring  to  light  many  most 
interesting  facts  about  the  history  of  the  disease  in 
the  records  of  Arctic  and  Antarctic  exploration. 
There  is  a  remarkable  contrast  between  two  expedi- 
tions, that  of  Sir  Robert  McClure  in  the  Investigator 
in  1850,  and  that  of  the  Alert  and  the  Discovery  in 
1875.  McClure  went  to  seek  for  Sir  John  Franklin  ; 
his  ship  was  north  of  Alaska  for  twenty-seven  months 
after  leaving  England  before  the  first  case  of  scurvy 
occurred,  in  spite  of  great  hardships  and  many 
months  on  half  rations.  In  the  Alert  and  Discovery, 
north  of  Greenland,  there  was  a  severe  outbreak  of 
scurvy  in  eleven  months,  though  on  full  rations. 
The  Alert  had  sixty  cases  and  three  deaths  out  of  a 
company  of  122.  The  food  supply  of  the  Alert  and 
of  the  Investigator  was  practically  the  same,  except 
that  on  the  latter  lemon-juice  was  used,  and  on  the 
Alert  lime-juice.  In  each  case  the  officers  took  great 
care  to  see  that  the  juice  was  really  drunk. 


10  FOOD    DEFICIENCY    DISEASES 

Finally,  an  investigation  has  been  made  experi- 
mentally by  Chick  and  Hume  at  the  Lister  Institute, 
which  shows  that  lemon- juice  has  four  times  the 
antiscorbutic  power  of  lime-juice.  Oranges  are  as 
good  as  lemons,  and  the  fruit  is  better  than  the 
bottled  juice.  The  antiscorbutic  power  of  fresh 
meat  is  low  ;  about  four  pounds  a  day  is  needed  in 
man,  whereas  an  ounce  of  lemon-juice  will  do.  The 
most  interesting  discovery  is  that  germinating  peas 
and  beans  develop  a  high  proportion  of  the  vitamine. 
If  they  are  soaked  in  water  for  twenty-four  hours, 
then  spread  out  to  germinate  for  two  days,  and 
cooked  not  longer  than  an  hour,  they  are  powerfully 
antiscorbutic.  V^^hat  suffering  it  would  have  saved  if 
this  had  been  known  before  !  The  Alert  and  Discovery 
brought  back  unused  6000  pounds  of  dried  peas  ! 

During  the  war  there  was  a  good  deal  of  scurvy 
amongst  Serbian  soldiers  in  Macedonia,  and  Wiltshire 
was  able  to  test  the  relative  curative  value  of  lemon- 
juice  and  of  germinated  beans  by  allotting  a  ward 
full  of  scorbutics  to  be  treated  by  each  method. 
In  spite  of  the  fact  that  the  soldiers  rather  resented 
being  fed  upon  *  pig-food',  its  therapeutic  virtues 
were,  if  anything,  rather  superior  to  those  of  the 
fruit-juice. 

Swedes,  potatoes,  and  cabbage,  unless  cooked  too 
long,  all  contain  the  antiscorbutic  vitamine.  Canned 
fruits  and  vegetables  are  almost  useless.  Beer  had 
a  great  reputation  in  the  old  Navy  ;  native  Kafhr 
beer  certainly  protects,  but  the  '  high-dried  kilned 
malt '  used  by  Sir  John  Franklin's  expedition,  and 
modern  brewed  beers,  are  of  no  value. 


FOOD    DEFICIENCY    DISEASES  11 

Fresh  milk  contains  the  vitamine,  but  it  is  lost 
on  boiling  for  more  than  five  minutes.  It  disappears 
in  stale  or  dried  milk.  Probably  this  vitamine  may 
fail  at  the  end  of  prolonged  lactation,  thus  accounting 
for  a  few  authentic  cases  of  scurvy  in  breast-fed 
babies.  In  ordinary,  sufferers  from  infantile  scurvy 
have  been  fed  on  stale,  artificial,  sterilized  foods. 
The  disease  is  rapidly  cured  by  giving  fresh  unboiled 
milk  and  fruit-juices.  Infants  reared  on  boiled  milk 
ought  to  have  a  little  orange-  or  grape-juice  (though 
this  is  not  quite  as  good)  every  few  days.  They 
like  it.  Also,  the  milk  ought  not  to  be  boiled  more 
than  a  minute.  If  no  other  source  of  vitamine  is 
supplied,  animals  have  to  be  given  a  great  deal  of 
milk  to  avert  scurvy. 

The  vitamines  that  prevent  beri-beri  and  scurvy 
are  both  water-soluble,  but  they  are  not  identical. 
The  antineuritic  body  is  not  so  readily  destroyed  by 
heat,  and  it  keeps  better. 

RICKETS. 
Rickets  is  probably  another  deficiency  disease. 
The  infants  have  usually  been  fed  upon  a  diet  con- 
taining too  much  starch  and  sugar,  and  too  little  fat 
and  protein.  The  observations  of  Bland-Sutton  at 
the  London  Zoo  rather  point  to  the  deficiency  of  fat 
as  being  the  more  important.  A  lioness  there  was 
unable  to  suckle  for  long,  and  litter  after  litter  of  cubs 
had  died  of  rickets.  Investigation  of  the  diet  showed 
that  they  were  fed  upon  London  cab-horse,  which 
naturally  did  not  supply  any  fat,  and  their  little 
teeth  were  not  able  to  crush  the  bones  and  obtain  the 


12  FOOD    DEFICIENCY     DISEASES 

marrow.  When  they  were  given  milk,  cod-hver  oil, 
and  pounded  bones  they  did  excellently.  It  is  well 
known,  of  course,  that  cod-liver  oil,  cream,  and  fresh 
milk  are  the  best  treatment  for  rickets.  There  is 
considerable  difference  of  opinion  at  the  moment 
whether  rickets  is  due  principally  to  deprivation  of 
a  fat-soluble  vitamine,  as  the  above  observations 
and  the  researches  of  the  Mellanbys  would  indicate, 
or  to  lack  of  fresh  air  and  exercise,  as  is  maintained 
by  Noel  Paton  and  other  workers  in  the  Glasgow 
school.  At  the  Glasgow  Zoo,  cod-liver  oil  does  not 
prevent  rickets  ;  the  only  zoo  free  from  it  is  said 
to  be  Hagenbeck's  at  Hamburg,  where  the  animals 
are  allowed  great  open  spaces  and  natural  conditions. 
Investigation  of  the  home  surroundings  of  children 
of  the  hospital  class  in  Glasgow  shows  little  differ- 
ence as  to  bottle-feeding  and  breast-feeding,  or  the 
amount  of  fat  in  the  dietary,  between  the  healthy 
and  the  rickety.  If  the  rooms  were  small,  crowded, 
high  up,  and  ill-ventilated,  and  the  children  seldom 
taken  out,  the  proportionate  incidence  of  rickets 
was  high.  In  the  markedly  rachitic  children,  3*93 
persons  inhabited  each  room,  and  the  cubic  feet  of 
air-space  per  person  was  422  ;  in  the  non-rachitic, 
there  were  3  persons  per  room,  and  the  air-space 
was  625  cubic  feet.  The  homes  of  the  rachitic  were 
poorer  and  less  well  cared  for.  Of  the  rachitic, 
only  30  per  cent  were  properly  exercised  ;  of  the 
healthy,  86  per  cent. 

There  is  some  animal  evidence  in  the  same  direc- 
tion. Puppies  kept  in  the  laboratory  are  much 
more  prone  to  rickets  than  those  allowed  to  run  wild 


FOOD     DEFICIENCY     DISEASES  13 

in  the  country.  The  A-ray  signs  of  rickets  at  the 
growing  ends  of  a  puppy's  long  bones  are  very  well 
shown.  In  some  cases  the  country  puppies  were 
given  less  fat  than  the  laboratory  ones.  A  particular 
instance  is  quoted  of  two  identically  fed  puppies, 
one  belonging  to  an  active  boy  and  the  other  to  his 
invalid  cousin  ;  the  latter  developed  rickets,  because 
it  was  more  cooped  up. 

The  Mellanbys  maintain  the  vitamine  h}^othesis. 
E.  Mellanby  has  used  a  much  larger  number  of  pups, 
over  200,  and  finds  that  a  diet  containing  bread, 
meat,  oatmeal,  linseed  oil,  yeast,  orange-juice,  and 
an  inadequate  amount  of  milk  causes  rickets 
constantly  in  a  few  months.  Giving  more  milk,  or 
animal  fats,  prevents  rickets.  Fast-growing  pups 
show  symptoms  more  markedly  than  slow-growing. 
Calcium  salts  make  no  difference.  Whether  the 
vitamine  is  the  same  as  that  necessary  for  growth 
(fat-soluble  A)  is  not  certain.  Mrs.  Mellanby  shows 
that  on  such  a  diet,  adequate  in  all  other  respects, 
but  lacking  animal  fats,  the  puppies'  deciduous 
teeth  are  lost  late,  the  permanent  teeth  erupt  late 
and  are  badly  placed,  the  enamel  is  defective,  and 
the  calcium  content  low.  If  plenty  of  milk  or 
cod-liver  oil  is  given,  the  teeth  are  normal. 

Mellanby  replies  to  the  Glasgow  school,  that  the 
milk  allowance  for  their  dogs  was  always  rather  low, 
so  that  the  difference  between  confinement  and 
exercise  might  turn  the  scale  when  animals  were 
already  near  the  margin,  by  differences  in  appetite 
and  assimilation.  WTien  pups  have  plenty  of  milk, 
confinement    does    not    make    them    rickety.      The 


14  FOOD     DEFICIENCY    DISEASES 

amount  of  fat  in  the  dietary  of  the  Glasgow  children 
was  very  near  the  minimum,  and  there  was,  as  a 
matter  of  fact,  less  in  the  diet  of  the  rachitic  families  ; 
also,  if  children  eat  a  lot  of  bread  the}^  tend  to 
neglect  the  articles  that  contain  the  vitamine. 

There  are  other  facts  that  tell  in  favour  of  the 
vitamine  theory,  though  it  must  be  allowed  that 
Findlay  and  the  other  Glasgow  workers  have  taught 
us  a  lesson  as  to  the  importance  of  fresh  air  and 
exercise  in  the  prevention  of  rickets.  In  an  American 
negro  baby  clinic,  of  thirty-two  infants  given  54  oz. 
of  cod-liver  oil  in  six  months,  only  two  were  rachitic  ; 
of  sixteen  given  none,  all  but  one  became  rickety. 
Experience  surely  teaches  that  milk,  cream,  and 
cod-liver  oil  are  curative,  but  probably  we  have 
overdone  the  splinting  for  bow-legs  and  knock-knee  ; 
it  would  be  better  to  straighten  the  bones  under  an 
anaesthetic  and  get  them  running  about  in  the  open 
air  as  soon  as  possible.  In  Greenland,  where  the 
Eskimo  children  are  cooped  up  all  the  winter  in 
huts  but  get  plenty  of  animal  fat,  rickets  does  not 
occur. 

In  constructing  a  diet  table  for  children  it  ought 
to  be  remembered  that  such  a  deficiency  of  vitamines 
as  may  produce  scurvy,  beri-beri,  rickets,  or  stunted 
growth  represents  a  gross  deviation  from  the  ideal, 
and  that  much  chronic  ill-health  and  liability  to 
infection  may  result  from  less  exaggerated  deviations. 


FOOD    DEFICIENCY    DISEASES  15 

REFERENCES.* 

Funk. — Brit.    Med.    Jour.,     1913,    i,  814;    and    articles  in 
Journal  of  Physiol.,  1911-13. 

Hopkins. — Proc.   Royal   Soc.   Med.  (Therapeutical   Section), 
vol.  vii,  Nov.,   1913,   I  ;   Brit.  Med.  Jour.,   1919,  i,  507. 

Halliburton  and  Drummond. — Jour,  of  Physiol.,  1917,  li, 
235- 

Alice   Henderson   Smith. — Jour.    R.A.M.C.,    1919,    xxxii, 
93,  188  ;    Lancet,  1918,  ii,  813, 

Wiltshire. — Lancet,  19 18,  ii,  811. 

Findlay. — Glasgow  Med.  Jour.,  1918,  268. 

Mellanby. — Lancet,   1919,  i,  407. 

Chick  and  Hume. — Lancet,  1919,  ii,  320. 


*  References  at  the  end  of  chapters  are  not  meant  to  be  exhaus- 
tive. Only  a  few  accessible  authorities  are  quoted,  in  some  of 
which  a  fuller  bibliography  will  be  found. 


16 


CHAPTER   II, 
RESEARCHES     ON     BLOOD. 

RECOVERY    OF    BLOOD    AFTER    HEMORRHAGE BLOOD    TRANS- 
FUSION  THE      FOUR      BLOOD       GROUPS— FATE      OF      RED 

BLOOD-CORPUSCLES — FUNCTIONS  OF  THE  SPLEEN  AND 
LIVER— COAGULATION  OF  THE  BLOOD PURPURA  HEMOR- 
RHAGICA   HEMOPHILIA ANAPHYLAXIS THE  THERA- 
PEUTICS   OF   CALCIUM    SALTS. 

THROUGHOUT  the  Great  War  haemorrhage  has 
been  a  terrible  bugbear.  Not  only  did 
wounded  men  often  lose  a  dangerous  amount  of 
blood  before  they  could  be  collected  from  the  forward 
areas  and  be  brought  to  the  nearest  medical  officer, 
but  the  surgeon's  ancient  enemy,  secondary  haemor- 
rhage, which  in  civil  practice  had  almost  ceased  to 
interest  us  on  account  of  its  rarity,  became  a  common 
and  deadly  foe  once  more.  There  is  no  doubt  that 
the  study  of  the  blood  and  its  problems  had  made 
greater  advance  in  America  than  in  the  British 
Isles,  and  the  valuable  assistance  of  American 
medical  officers,  coming  at  a  time  when  we  were  all 
thinking  about  such  problems,  has  led  to  a  better 
understanding  of  many  important  facts. 

We  shall  consider  first  the  process  of  natural 
recovery  from  a  big  haemorrhage.  It  has  long  been 
known  that  within  a  few  minutes  the  blood  remain- 
ing in  the  vessels  becomes  diluted  by  taking  up 
watery  fluid  from  the  tissues,  and  that  the  arteries 


RESEARCHES    ON    BLOOD  17 

contract  down  on  the  reduced  volume  so  as  to 
maintain  the  blood-pressure  and  provide  an  efficient 
filling  for  the  heart  on  the  venous  side.  We  now 
know  that  there  is  active  spasm  of  the  veins  also, 
so  much  so  that  there  may  be  serious  difficulty  in 
getting  an  intravenous  infusion  to  flow.  I  have 
several  times  during  a  blood  transfusion  been 
compelled  to  use  the  internal  saphenous  vein  at  the 
groin  on  this  account. 

There  are  several  modem  methods  of  estimating 
the  total  blood-volume.  The  best  is  by  the  use  of 
an  innocuous  dye  called  '  vital  red',  introduced  by 
Keith,  Rowntree,  and  Geraghty.  A  sample  of  the 
patient's  plasma  (lo  c.c.)  is  first  obtained,  citrated, 
and  centrifugalized — or  another  person's  plasma 
will  do.  Then  a  dose  of  the  dye,  well  diluted,  is 
given  intravenously  (3  mgrms.  per  kilo  of  body 
weight).  Two  samples  of  blood  are  then  taken 
three  and  six  minutes  after  from  the  two  arm  veins  ; 
these  are  citrated  and  centrifugalized.  The  original 
plasma  diluted  with  three  parts  of  saline  is  then 
mixed  with  the  dye  solution  to  match  the  coloured 
plasma,  withdrawn  after  injection,  in  a  colorimeter. 
From  this  the  plasma-volume  in  the  body  can 
be  calculated.  To  obtain  the  whole-blood-volume, 
a  haemocrit  must  be  used.  In  normal  persons  the 
plasma-volume  is  one-twentieth  the  body  weight, 
and  the  blood- volume  is  one-twelfth  the  body  weight. 
This  is  a  higher  figure  than  that  obtained  by  the 
older,  less  accurate,  and  more  dangerous  carbon- 
monoxide  method,  but  it  agrees  well  with  the  results 
got  by  another  procedure — that  is,  by  calculating 

2 


18  RESEARCHES     ON    BLOOD 

from  the  difference  in  the  blood-count  before  and 
after  transfusing  with  a  known  volume  of  gum- 
acacia  solution. 

In  obesity  the  plasma-volume  is  relatively  low, 
and  in  chlorosis  relatively  high  ;  it  is  also  high  late 
in  pregnancy. 

After  a  severe  haemorrhage,  the  total  blood-volume 
may  fall  to  60  per  cent  of  the  normal,  and  yet  recovery 
may  take  place.  Insisting  on  the  patient  taking 
large  quantities  of  fluids  by  the  mouth  and  per 
rectum  greatly  hastens  the  rate  of  recovery.  In  a 
few  cases  the  capillary  haemoglobin-count  was  higher 
than  the  venous  (30  per  cent  and  26  per  cent)  ;  as 
the  patient  improves,  the  difference  passes  off 
(Robertson  and  Bock). 

During  the  process  of  regeneration,  the  red  marrow, 
which  is  normally  confined  to  the  flat  bones,  the 
bodies  of  the  vertebrae,  and  the  ends  of  the  long 
bones,  encroaches  upon  the  yellow  marrow  in  the 
shafts  of  the  long  bones  to  some  extent.  A  few 
nucleated  reds  may  turn  up  in  the  peripheral 
circulation.  A  much  more  constant  sign  of  blood- 
regeneration  is  the  appearance  amongst  the  red 
corpuscles  of  reticulated  cells,  best  seen  after 
staining  \\ith  cresyl-blue,  which  may  be  used  instead 
of  Hayem's  fluid  for  the  blood-count.  In  normal 
blood  these  cells  amount  to  i  per  cent ;  during 
active  blood-regeneration  they  may  reach  20  per 
cent. 

Kerr,  Hun\itz,  and  Wliipple  have  made  a  study  of 
the  restoration  of  the  blood-serum  proteins.  If  after 
a  big  bleeding  the  red  corpuscles  are  centrifugaUzed 


RESEARCHES    ON    BLOOD  19 

off,  suspended  in  Locke's  fluid,  and  returned  to  the 
circulation  (in  dogs),  it  takes  some  weeks  to  restore 
the  protein  to  normal.  If  the  animal  is  starved, 
recovery  is  retarded.  If  plenty  of  meat  is  given, 
however,  the  restoration  will  be  speeded  up,  and  a 
50  per  cent  depletion  may  be  recovered  from  in  five 
to  seven  days.  There  is  some  evidence  that  the  new 
protein  is  supplied  by  the  liver.  In  a  dog  in  which 
the  liver  has  been  partly  cut  out  of  the  circulation 
by  an  Eck  fistula,  recovery  of  the  serum  protein 
after  bleeding  is  slow  and  poor.  In  phosphorus 
poisoning,  reduction  of  the  liver  protein  and  serum 
protein  go  together. 

BLOOD     TRANSFUSION. 

It  has  passed  into  a  hackneyed  phrase  to  speak  of 
'  infusing  new  blood '  into  a  committee  or  business 
undertaking  ;  but  until  the  last  two  years  of  the 
war  the  procedure  has  been  more  metaphorical  than 
literal  in  Great  Britain.  In  America,  blood  trans- 
fusion has  made  immense  strides.  There  is  no 
doubt,  now  that  so  many  medical  officers  have 
learned  its  value  in  France,  that  it  will  become  a 
well-estabhshed  method  of  treatment  in  this  country. 

It  is  well  known  that  animal's  blood,  or  preserved 
serum,  cannot  be  used,  as  violent  toxic  symptoms 
are  produced  if  any  considerable  quantity  is 
injected. 

The  principal  indication  for  blood  transfusion  is  a 
severe  haemorrhage  of  whatever  origin.  For  this 
condition  the  benefit  is  very  striking — much  more 
lasting  than  that   seen   after  a  saline  transfusion. 


20  RESEARCHES    ON    BLOOD 

Traumatic  shock  apart  from  haemorrhage  is  also 
improved  by  injecting  blood.  For  these  purposes 
one  needs  large  quantities  ;  about  a  pint  is  a  usual 
dose.  Blood  transfusion  is  probably  the  best 
remedy  we  know  for  pernicious  anaemia,  but  it  is 
not  a  permanent  cure.  It  appears  to  act  not  so 
much  by  directly  increasing  the  volume  and  oxygen- 
carrying  power  of  the  blood,  but  by  stimulating  the 
red  marrow  to  renewed  activity,  and  so  to  bring  on 
a  remission.  Yet  another  indication  is  continuing 
haemorrhage  from  haemophilia,  as  we  shall  see.  For 
these  two  diseases,  half  a  pint  will  be  sufficient  as 
a  dose. 

Many  different  methods  are  in  use  for  giving  the 
blood.  I  have  described  these  in  some  detail  else- 
where. Direct  arm-to-arm  transfusion  by  connect- 
ing the  donor's  artery  with  the  patient's  vein  is 
unsatisfactory  in  that  one  does  not  know  how  much 
blood  passes  ;  it  may  be  little  or  none.  Some  prefer 
to  use  unmodified  blood  kept  from  clotting  by  with- 
drawing from  a  vein  into  a  paraffin-lined  receptacle 
and  injected  as  quickly  as  possible.  Others  prefer 
to  use  citrated  blood,  which  is  much  easier  to  handle. 
I  have  given  much  larger  doses  of  citrate  intra- 
venously to  wounded  soldiers  than  we  now  consider 
necessary,  and  no  harm  resulted.  Hedon  finds  that 
4  grms.  is  safe  for  a  dog.  I  have  several  times 
given  8  or  9  grms.  to  men.  It  is  a  curious  point 
that  the  injection  of  citrate  does  not  alter  the 
coagulation  time  of  the  receiver's  blood  ;  this  has 
been  verified  by  myself  and  others.  It  is  also 
interesting  that  taking  a  pint  of  blood  from  a  healthy 


RESEARCHES    ON    BLOOD  21 

donor  docs  not  produce  any  symptoms.  In  America 
there  are  professional  donors  who  are  wilhng  to  give 
blood  once  every  three  weeks  or  so. 

A  very  interesting  research  has  been  published 
by  Abel  that  has  borne  good  fruit  during  the  war. 
He  found  in  animals  that  a  big  haemorrhage  can  be 
replaced  just  as  efficiently  by  the  animal's  red  blood- 
corpuscles  washed  and  suspended  in  Locke's  fluid 
as  by  fresh  whole  blood.  The  plasma  proteins  do 
not  seem  to  matter.  Rous  and  Turner  carried  the 
matter  further,  and  showed  that  red  corpuscles 
kept  in  a  citrate-dextrose  solution  may  be  preserved 
in  an  ice-chest  for  several  wrecks,  and  will  still  func- 
tion if  injected  into  an  animal  of  the  same  species 
at  the  end  of  that  time.  If  they  are  kept  too  long 
(three  weeks  in  a  rabbit,  over  four  weeks  in  a  man), 
they  do  no  harm,  but  are  rapidly  removed,  so  that 
if  the  receiving  animal  is  bled,  and  then  transfused 
with  the  preserved  corpuscles,  the  blood-counts 
show  first  the  rapid  fall  due  to  the  bleeding,  then 
the  rise  to  normal  following  transfusion,  then  in 
the  course  of  a  few  days  a  rapid  fall  to  the  post- 
haemorrhage  level.  If  the  corpuscles  have  not  been 
kept  too  long  and  are  still  functioning,  this  secondary 
fall  does  not  occur. 

Captain  O.  H.  Robertson  was  sent  to  the  casualty 
clearing  station  where  I  was  working  just  before  the 
battle  of  Cambrai,  to  apply  these  results  to  man. 
Forty  pints  of  blood  (including  a  pint  from  a  well- 
known  surgeon)  were  taken  and  stored  in  ice,  in  a 
citrate-dextrose  solution.  It  takes  about  a  week 
for  the  corpuscles  to  settle  ;   the  supernatant  plasma 


22  RESEARCHES    ON    BLOOD 

is  then  decanted  off.  The  results  were  just  as  good 
as  those  obtained  by  using  fresh  blood.  Needless 
to  say  it  might  be  dangerous  to  inject  plasma  which 
had  been  kept  any  length  of  time. 

Miss  Ashby  has  shown  that  after  a  blood  trans- 
fusion the  injected  red  corpuscles  survive  at  least 
thirty  days  in  man.  This  was  determined  by 
transfusing  a  patient  belonging  to  Group  II  with 
Group  IV  cells,  and  then  testing  by  agglutinins 
for  the  Group  IV  cells  at  various  dates  after- 
wards. 

Blood  transfusion  in  man  is  not  completely  devoid 
of  risks  to  the  receiver.  There  is  the  possibility  of 
conveying  disease,  such  as  syphilis,  if  the  donor  is 
not  healthy.  A  rigor  may  follow,  or  vomiting,  or  a 
rise  of  temperature.  If  the  transfusion  is  given  too 
fast,  the  patient  may  complain  of  a  feeling  of  disten- 
tion and  bursting  inside  the  chest.  The  most 
serious  danger,  however,  arises  from  the  use  of  an 
incompatible  blood.  If  the  donor  and  the  patient 
do  not  belong  to  the  same  blood  groups,  there  may 
be  haemolysis  of  the  injected  corpuscles,  resulting 
in  vomiting,  dyspnoea,  an  urticarial  rash,  a  quick 
weak  pulse,  and  perhaps  con\ailsions  or  coma. 
These  may  come  on  during  the  transfusion,  and 
may  be  followed  by  haemoglobinuria.  In  a  few 
cases  death  has  resulted.  If  the  transfusion  is 
stopped  immediately,  serious  trouble  may  be  averted. 
This  brings  up  the  importance  of  testing  out  the 
donor  beforehand.  If  this  precaution  is  not  taken, 
alarming  reactions  may  be  expected  in  5  to  lo  per 
cent  of  the  cases. 


RESEARCHES    ON    BLOOD 


23 


THE     FOUR     BLOOD    GROUPS. 

Strange  to  say,  the  bloods  of  different  individuals, 
even  of  the  same  family,  are  not  always  compatible. 
Shortly  after  birth  the  blood  takes  up  the  characters 
of  one  of  four  groups,  and  these  apparently  persist 
throughout  life  unchanged.  The  blood  of  a  person 
of  a  particular  group  may  safely  be  given  to  another 
person  of  that  group,  but  not  necessarily  to  someone 
belonging  to  another  group.  The  incompatibility 
lies  in  two  directions  :  the  one  plasma  will  (i)  haemo- 
lyze  and  (2)  agglutinate  the  corpuscles  of  a  patient 
of  another  group.  It  seems  to  be  established  that 
a  blood  which  will  haemolyze  another  will  always 
agglutinate  it ;  this  is  convenient,  because  it  is 
simpler  to  test  out  the  agglutination  reaction  than 
the  haemolysis. 

According  to  Moss,  there  are  four  classes  of  bloods, 
designated  as  Groups  /,  //,  ///,  and  IV.  The 
relative  frequency  of  these  groups,  and  their  suit- 
ability as  donors,  are  given  in  the  following  table  : — 


Donor 

Percentage 
frequency. 

Suitable  if  patient 
belongs  to 

Group    I 
.,       II 
.,       Ill 
,.       IV 

5 
40 
10 
45 

Group    I 

,.     I.  II 
„     I,  III 

„       I,  II,  III,  IV 

When  the  blood  of  a  Group  IV  donor  is  given  to  a 
Group  I,  II,  or  ///  patient,  the  plasma  of  the  donor 
has  a  tendency  to  haemolyze  and  agglutinate  the 
corpuscles  of  the  patient  ;    but  the  plasma  of  the 


24  RESEARCHES     ON    BLOOD 

patient  does  not  so  act  on  the  corpuscles  of  the 
donor,  and  it  is  found  in  practice  that  what  matters 
is  the  effect  of  the  patient's  plasma  on  the  injected 
corpuscles,  not  the  reverse.  This  is  no  doubt  because 
the  bulk  of  the  patient's  blood  is  so  much  greater 
than  that  of  the  transfused  blood. 

The  best  method  of  determining  the  blood  group 
of  a  donor  is  by  the  use  of  preserved  stock  sera 
belonging  to  Groups  II  and  ///.  To  make  the  test, 
a  glass  slide  is  taken,  and  a  large  drop  of  the  test 
serum  placed  one  near  each  end.  Then  the  donor's 
ear  is  pricked,  and  a  small  drop  of  blood  taken  with 
a  match-stick  and  mixed  with  the  Group  II  serum. 
Another  drop  is  mixed  by  another  match-stick  with 
the  Group  III  serum.  The  result  may  be  as 
follows  : — 


Blood  Corpuscles  agglutinated  by 

Donor  is 

Group    II  and  Group  III  serum 

,,     III  serum  but  not  Group  II  serum 
,,       II  serum  but  not  Group  III  serum 

Neither  serum 

Group    I 

,.        II 
„       III 
,.       IV 

The  agglutination  is  quite  obvious  to  the  naked  eye 
in  about  five  minutes. 

In  choosing  donors,  we  may  use  either  9ne  belong- 
ing to  the  same  group  as  the  patient,  or  a  Group  IV 
donor.  Groitp  IV  individuals  are  the  universal 
providers.  Thus,  if  a  Group  IV  donor  is  available, 
it  is  not  necessary  to  know  what  group  the  patient 
belongs  to.  On  the  other  hand,  if  both  patient  and 
donor  belong  to  Group  II,  the  bloods  will  be 
compatible. 


RESEARCHES    ON    liLOOD  25 

If  one  has  not  the  two  group  sera  in  stock,  it  is 
necessary  to  test  the  patient's  serum  against  the 
donor's  corpuscles  directly.  Draw  off  a  few  c.c.  of 
the  patient's  blood  and  allow  it  to  clot  in  a  tube. 
Obtain  a  large  drop  of  quite  clear  serum,  add  a  trace 
of  citrate,  and  then  mix  in  a  small  drop  of  the  donor's 
blood.  If  agglutination  occurs  in  five  minutes,  the 
donor  is  unsuitable  ;  if  there  is  no  agglutination, 
the  donor's  blood  may  be  used  for  that  patient. 

FATE     OF     RED     BLOOD-CORPUSCLES. 

Some  of  the  older  text-books  hazard  a  guess  that 
red  blood-corpuscles  usually  live  about  three  weeks, 
but  since  even  transfused  corpuscles  in  man  are 
surviving  after  a  month  it  is  probable  that  the 
ordinary  life  of  a  corpuscle  is  much  longer.  The 
normal  fate  of  red  cells  in  man,  monkeys,  and  cats, 
according  to  Robertson  and  Rous,  is  to  fragment 
in  the  blood-stream,  and  the  fragments  are  swept 
up  by  the  spleen.  The  poikilocytes  and  microcytes 
of  grave  anaemia  do  not  appear  to  be  preformed  in 
the  red  marrow,  and  they  are  the  result  of  breaking 
up  of  circulating  red  corpuscles.  Often  they  show 
the  reticulum  which  is  characteristic  of  young  cells. 

In  the  dog,  rat,  and  guinea-pig,  whole  red  cor- 
puscles are  taken  up  by  the  spleen. 

FUNCTIONS  OF  THE  SPLEEN  AND  LIVER 
IN  RELATION  TO  THE  BLOOD. 

It  has  been  known  for  years  that  the  spleen  must 
have  some  relation  to  the  formation  or  destruction 
of  blood- corpuscles.     The  way  in  which  it  enlarges 


26  RESEARCHES     ON    BLOOD 

in  blood  diseases  such  as  leukaemia,  pernicious 
anaemia,  von  Jaksch's  anaemia,  splenic  anaemia, 
chronic  malaria,  and  other  tropical  blood-parasite 
infections,  is  proof  of  this.  Spleen  pulp  cells  can 
be  seen  in  the  act  of  immolating  damaged  red 
corpuscles.  But  when  we  seek  for  further  evidence, 
it  becomes  very  dubious  and  uncertain,  and  a  good 
many  of  the  published  observations  are  demonstrably 
incorrect. 

The  whole  subject  has  recently  been  re-investigated 
with  care  and  restraint  by  Pearce  and  his  fellow- 
workers,  taking  account  both  of  experimental  and 
clinical  observations. 

Splenectomy  in  dogs  gives  rise  to  the  following 
changes  : — 

1.  A  mild  secondary  anaemia  of  the  usual  type, 
reaching  its  maximum  after  a  month,  and  recovering 
later.  Why  this  occurs  is  unknown,  except  that 
injection  of  spleen- extract  into  a  normal  dog  causes 
a  brief  rise  of  the  red  count  by  stimulating  bone- 
marrow.  This  may  furnish  some  experimental 
basis  for  spleen- extract  therapy  in  anaemia. 

2.  A  brief  polymorphonuclear  leucocytosis.  Many 
other  leucocvte  variations  have  been  described,  but 
they  are  inconstant. 

3.  Increased  resistance  of  the  red  corpuscles  to 
haemolytic  agents.     We  do  not  know  why. 

4.  Reduced  liability  to  jaundice  and  haemo- 
globinuria  after  the  administration  of  haemolytic 
agents.  This  may  be  due  to  three  factors.  The 
animal  being  anaemic,  the  death-rate  amongst  the 
red  cells  is  low,  and  the  liver,  the  grave-digger  in 


RESEARCHES    ON     BLOOD  27 

ordinary  when  the  spleen  is  gone,  is  not  Hkely  to 
be  overworked  even  when  the  death-rate  rises  some- 
what. Again,  the  corpuscles  are  more  resistant. 
And  thirdly,  as  the  spleen  and  splenic  vein  are  gone, 
the  liver  receives  less  blood. 

The  point  is  interesting,  because  we  know  that 
there  are  two  varieties  of  splenomegaly  associated 
with  anaemia  and  jaundice.  One  variety  is  con- 
genital, the  other  is  acquired.  In  each,  splenectomy 
cures  the  anaemia  and  the  jaundice.  Probably  the 
spleen  contained  a  haemolytic  toxin. 

In  spite  of  older  statements  to  the  contrary,  there 
is  no  constant  difference  in  the  cell-counts  of  the 
blood  of  the  splenic  artery  and  splenic  vein,  and  no 
free  haemoglobin  in  the  vein.  Nor  does  splenectomy 
in  normal  dogs  cause  metabolic  changes.  In  man, 
splenectomy  for  a  very  large  spleen  reduces  the 
excessive  output  of  uric  acid  and  urobilin. 

Diversion  of  the  splenic  vein  into  the  inferior 
vena  cava,  to  avoid  the  liver,  has  approximately 
the  same  effects  in  every  way  as  splenectomy. 

In  most  cases  after  removing  the  spleen  the  yellow 
marrow  in  the  shaft  of  the  femur  becomes  red, 
signifjdng  increased  production.  This  takes  about 
six  months.  The  reason  is  unknown.  The  haemo- 
lymph  glands  contain  an  excess  of  endothelial  cells, 
and  if  a  haemolytic  agent  is  given,  these  cells  are 
abnormally  full  of  red  corpuscles  in  process  of 
digestion.  Probably  this  is  compensatory.  A  new 
induced  anaemia  in  a  splenectomized  animal  is  badly 
recovered  from. 

Banti's  disease  is  supposed  to  be  a  chronic  inflam- 


28  RESEARCHES    ON    BLOOD 

mation  of  the  spleen  with  great  enlargement  (going 
on  later  to  fibrosis)  and  excessive  function,  so  that 
too  many  red  corpuscles  are  destroyed.  Splenec- 
tomy in  the  early  stages  cures  the  anaemia. 

Not  much  has  been  added  to  our  knowledge  of 
the  blood-destroying  functions  of  the  liver.  After 
Eck's  fistula,  the  liver  cells  atrophy  considerably, 
and  bilirubin  is  considerably  reduced  in  the  bile, 
which  suggests  that  the  liver  is  normally  active  in 
blood  destruction,  and  does  not  merely  sweep  up 
dead  and  degenerated  red  corpuscles.  Splenectomy 
does  not  alter  this  effect  (Wliipple  and  Hooper). 

COAGULATION     OF     THE     BLOOD. 

We  are  still  far  from  a  clear  conception  of  the 
exact  pathology  of  haemophiHa,  purpura,  and  the 
haemorrhagic  tendency  in  jaundice,  but  it  will 
be  only  by  a  sound  understanding  of  the  normal 
processes  of  coagulation  of  the  blood  that  we  shall 
be  able  to  comprehend  the  abnormal. 

The  phenomena  of  blood-clotting  are  beautifully 
designed  to  avoid  two  opposing  evils  :  if  no  provision 
was  made  for  fibrin  formation,  every  injury  would  be 
fatal ;  but  on  the  other  hand,  if  all  the  essentials  for 
the  process  were  already  present  in  the  plasma,  the 
circulation  would  immediately  be  brought  to  a 
standstill  by  intravascular  thrombosis.  Therefore 
coagulation  is  made  to  be  dependent  on  contact  with 
damaged  cells,  either  tissue-cells  or  leucocytes,  and 
in  particular  with  the  nucleoprotein  constituting 
their  nuclei,  while  the  intact  lining  endothelium  of 
the  blood-vessels  has  the  power  of  preventing  clotting. 


RESEARCHES    ON    BLOOD  29 

We  have  all  been  told  that  a  length  of  jugular  vein 
containing  blood  may  be  tied  at  each  end  and  hung 
up  for  a  week,  and  no  clotting  occurs  until  damaged 
tissue-cells  are  added.  Thus  we  find  that  the  very 
incision  or  laceration  which  excites  the  haemorrhage 
provides  also  the  wherewithal  to  stop  it.  The 
nucleoprotein  furnished  in  this  way  by  the  tissues  is 
called  thromhokinase. 

Next,  we  know  that  calcium  salts  are  needful  for 
clotting,  and  if  they  are  withdrawn  by  oxalates  or 
citrates,  no  fibrin  will  be  formed.  An  excess  of 
calcium  salts,  however,  delays  clotting. 

Concerning  thromhogen  or  prothrombin  we  cannot 
speak  so  confidently.  It  is  intimately  associated 
with,  and  hard  to  separate  from,  fibrinogen,  but  is 
probably  derived  eventually  from  the  leucocytes 
and  platelets.  Hydrocele  fluid,  which  does  not 
contain  any  corpuscles,  will  not  clot  until  blood  or 
fibrin  is  added. 

The  actual  mother  substance  of  the  fibrin  is  of 
course  the  fibrinogen,  a  protein  in  the  plasma.  There 
is  really  a  double  reaction,  thus  : — 

(i)  Prothrombin       +     Thrombokinase    +     Calcium  salts 
(  =  thrombogen)        (from  damaged  (in  plasma) 

(?  from  leucocytes)      leucocytes  or 
tissue-cells) 

I I ^1 

I 
Thrombin  (  =  fibrin  ferment) 

(ii)      Thrombin  +  Fibrinogen  (in  plasma) 

i  I 


Fibrin 
According  to  J.  Mellanby,  the  name  fibrin  ferment 


30  RESEARCHES    ON    BLOOD 

is  a  misnomer,  as  a  particular  weight  of  thrombin 
will  liberate  only  a  certain  definite  quantity  of  fibrin 
from  fibrinogen,  whereas  a  ferment  knows  no  limits 
to  its  activities. 

We  have  yet  one  more  provision  to  refer  to.  The 
cells  lining  the  blood-vessels,  and  the  leucocytes 
themselves,  are  not  immortal.  When  they  die, 
thrombokinase  is  shed  out,  and  so  thrombin  would 
be  formed  and  induce  local  clotting.  This  does 
actually  occur  in  phlebitis  and  other  forms  of 
venous  or  arterial  thrombosis.  In  the  physiological 
state,  however,  the  liver  secretes  into  the  blood  an 
antithromhin  sufficient  in  amount  to  deal  with  small 
formations  of  thrombin,  but  not  sufficient  to  interfere 
with  the  natural  process  of  arrest  of  haemorrhage. 

Recent  research  suggests  that  antithromhin  is  the 
product  of  interaction  of  two  other  substances, 
called  heparin,  which  is  derived  from  the  liver,  and 
proantithrombm.  Both  are  said  to  be  present  in  the 
blood.  The  heparin  activates  the  proantithrombin 
when  it  is  needed  (Howell). 

Considerable  variations  take  place  in  the  readiness 
with  which  the  blood  coagulates,  and  it  is  often  easier 
to  understand  why  than  how  this  is  brought  about. 
For  instance,  at  the  end  of  pregnancy  clotting  is 
rapid  ;  in  the  diseases  mentioned  above  it  is  deficient 
or  slow.  After  a  haemorrhage,  the  fibrinoplastic 
(clot-forming)  power  rises  quickly.  Information  may 
be  obtained  by  means  of  the  coagulimeier,  a  standard 
capillary  tube  into  which  the  blood  is  sucked  up  so 
that  the  time  which  it  takes  sohdifj^ng  may  be 
measured.     It  requires  some  care  in  practice  to  avoid 


RESEARCHES    ON    BLOOD  31 

variations  in  the  calibre,  variations  in  temperature, 
the  inclusion  of  lymph  or  clots,  etc. 

Associated  with  deficient  coagulability  there  is 
often  a  tendency  to  effusions  of  plasma  through  the 
capillary  walls  on  account  of  the  low  \dscosity  of  the 
blood.  The  symptoms  of  such  a  tendency  to  effusion 
are  liabihty  to  chilblains,  headaches,  nettlerash  or 
patchy  oedema,  and  transient  or  functional  albu- 
minuria. 

The  conversion  of  fibrinogen  into  fibrin  is  only  the 
first  stage  of  a  more  prolonged  process,  just  as  the 
very  similar  conversion  of  caseinogen  in  milk  into 
solid  casein  is  only  one  step  in  the  process  of  break- 
ing it  do\\'n  to  simpler  substances  such  as  peptones 
and  aminoacids. 

The  fibrin  is  not  a  permanent  body.  Even  in 
blood-clot  kept  at  about  40°  C.  it  undergoes  partial 
resolution  into  simpler  and  soluble  substances,  under 
the  influence  of  ferments  already  present  in  the  clot, 
called  fibrmolysins.  It  is  probable  that  these,  as 
well  as  leucocytes,  play  an  important  part  in  deter- 
mining the  resolution  of  fibrin  collections  in  the 
human  body,  such  as  may  be  found  not  only  in 
bruises  and  thromboses  but  also  in  the  lymph-clot 
which  is  the  precursor  of  adhesions  in  the  pleural 
and  peritoneal  cavities.  It  is  well  known  that  these 
adhesions  may  disappear  spontaneously  to  a  remark- 
able degree.  Any  value  which  thiosinamine  and  its 
derivative  fibrolysin  may  have,  given  hypodermically 
to  absorb  young  fibrous  tissue,  may  possibly  be  due 
to  the  production  of  ferments  such  as  these. 


32  RESEARCHES    ON    BLOOD 

PURPURA     HiEMORRHAGICA. 

English  physiologists  have  expressed  a  good  deal 
of  doubt  as  to  the  very  existence  of  platelets  as 
preformed  elements  in  the  blood.  It  is  said  that 
the  number  to  be  found  in  a  stained  film  depends 
upon  the  method  of  preparation,  and  that  when 
blood  stands  and  clots  it  deposits  platelets  in  plenty. 
It  is  also  said  that  they  are  never  visible  in  the  living 
circulation  in  the  web  of  a  frog's  foot  or  in  dog's 
omentum.  American  haematologists,  on  the  other 
hand,  seem  to  have  no  doubts  as  to  their  existence 
preformed  in  the  living  blood. 

Lee  and  Minot,  whilst  admitting  that  they  do  not 
occur  except  in  mammals,  say  that  platelets  are 
visible  in  the  circulating  blood  of  the  rabbit  or 
guinea-pig.  They  are  derived  from  the  mega- 
karyocytes of  the  marrow.  The  number  of  platelets 
present  runs  parallel  with  the  coagulability  of  the 
blood,  and,  in  particular,  blood-clot  will  not  retract 
firmly  so  as  to  plug  vessels  unless  platelets  are 
present  in  normal  numbers.  Benzol  reduces  the 
platelet  count,  and  may  lead  to  a  tendency  to  bleed. 
In  purpura  haemorrhagica,  and  the  haemorrhagic 
type  of  some  fevers,  the  platelets  are  few  or  absent 
in  the  blood. 

An  observation  that  is  interesting  in  itself,  and 
also  may  throw  light  on  the  platelet  problem,  is 
published  by  Lee  and  Robertson,  and  also  by 
Ledingham  and  Bedson.  If  the  platelets  are 
separated  out  from  guinea-pig's  blood  by  sedimenta- 
tion, and  injected  into  some  other  species,  such  as 
the  rabbit,   an  antibody  is  formed  in  the  rabbit's 


RESEARCHES     ON    BLOOD  33 

senim  destructive  to  guinea-pig's  platelets.  If 
some  of  the  serum  thus  obtained  is  injected  into  a 
guinea-pig,  a  condition  closely  resembling  purpura 
ha^morrhagica  is  produced.  There  are  bleedings 
from  the  nose,  bowel,  and  other  mucous  membranes, 
and  purple  patches  of  hiemorrhage  in  the  skin 
and  conjunctiva\  The  animal  may  die.  Few  or  no 
platelets  are  to  be  found  in  its  blood. 

It  is  not  suggested,  of  course,  that  the  disease  in 
man  is  produced  just  in  this  way,  but  the  experiment 
raises  the  probability  that  the  underlying  cause  of 
purpura  ha^morrhagica  may  be  a  toxin  destroying 
the  platelets,  which  as  we  have  seen  are  markedly 
reduced.  The  blood  in  this  disease  may  begin  to 
clot  in  normal  time,  but  the  coagulum  is  soft  and 
will  not  retract  firmly. 

HiEMOPHILIA. 
Of  all  the  many  conditions  in  which  the  h^emor- 
rhagic  diathesis  is  present,  haemophilia  is  at  once  the 
most  interesting,  the  best  understood,  and  the  most 
tragically  dangerous.  We  will  not  stay  to  speak  of 
the  curious  problems  of  its  inheritance,  nor  of  the 
well-known  tendency  to  bruising,  joint  effusions,  and 
bleeding  after  the  most  trivial  injuries.  One  or  two 
of  its  peculiarities,  however,  deserve  a  word  of 
mention,  as  they  may  throw  a  light  on  the  production 
of  the  haemorrhagic  tendency.  For  instance,  the 
locality  and  the  nature  of  the  injury  have  some 
significance.  In  a  few  cases,  wounds  below  the  neck 
may  not  bleed  to  excess,  whereas  abrasions  of  the 
most  trifling  description  affecting  the  lips,  cheeks. 


34  RESEARCHES    ON    BLOOD 

or  gums  may  baffle  all  attempts  to  stanch  the  flow. 
Again,  needle  pricks,  if  small,  do  not  bleed,  probably 
because  the  elastic  skin  seals  the  opening  ;  it  is 
even  safe  to  withdraw  blood  from  a  vein.  Further, 
it  is  not  true  that  the  haemorrhage  never  stops.  It 
may  cease  with  or  ^^^thout  treatment,  sometimes 
permanently,  sometimes  only  to  come  on  again  later. 
If  a  subcutaneous  haematoma  develops,  the  wall  is 
lined  by  well-formed  clot,  but  the  central  portion 
contains  blood  which  shows  no  tendency  to  coagu- 
lation in  spite  of  the  contact  with  clot.  It  is  the 
capillaries,  rather  than  the  arteries,  which  continue 
to  ooze. 

It  will  be  a  matter  of  opinion  whether  under  the 
generic  name  of  haemophilia  we  should  include  cases 
that  arise  every  now  and  then,  in  either  sex,  of  a 
congenital  and  persistent  tendency  to  bruise  and 
bleed  from  every  slight  abrasion,  apart  from  any 
family  history  of  a  similar  kind.  There  is  no  doubt 
that  the  symptoms  and  course  of  some  of  these  cases 
are  identical  with  ordinary  haemophiHa,*  and  they 
are  nearly  as  common.  Bulloch  states  that  the 
characteristic  joint  affections  never  occur  except  in 
the  hereditary  class. 

Up  to  a  certain  point  modern  observers  are  agreed 
as  to  the  cause  of  haemophilia.  Ever  since  Sir 
Almroth  Wright,  nearly  twenty  years  ago,  showed 
that  the  coagulation  time  in  these  patients  is  very 
greatly  delayed,  all  students  of  the  disease  who  have 
carefully  fulfilled  the  proper  conditions  have  been 


*  See   instances   given   by   Squire,   Brit.    Med.   Jour.,   1910,   i, 
p,  1168  ;   and  Osier,  Lancet,  1910,  i,  p.  1226. 


RESEAIUJIKS    ON     BLOOD  :i5 

able  to  establish  his  discovery.  Normal  blood  in  a 
Wright's  coagulimeter  tube  clots  in  5  to  10  minutes ; 
hccmophilic  blood  may  take  anything  from  15 
to  90  minutes  to  solidify,  although  the  eventual 
yield  of  fibrin  is  copious  and  firm.  Addis  has  shown 
that  the  coagulation  time  is  exactly  related  to  the 
severity  of  the  tendency  to  bleed,  the  mildest  cases 
yielding  the  shortest  times,  and  the  severe  cases  the 
longest.  It  is  true  that  a  few  who  have  used  the  blood 
shed  out  during  an  actual  hremorrhage  have  found 
no  delay  in  the  coagulation  time ;  but  apart  from 
other  fallacies,  such  as  the  danger  of  including  fibrin 
ferment,  the  mere  fact  of  the  continued  bleeding 
makes  the  blood  clot  more  rapidly  both  in  bleeders  and 
in  ordinary  people,  as  Wright  and  Addis  have  shown. 

Another  abnormality  in  the  blood  is  a  frequent 
deficiency  in  polymorphonuclear  leucocytes. 

We  may  take  it  that  the  rival  theory,  that  of  the 
undue  fragility  of  the  vessel  walls,  is  now  definitely 
abandoned.  Morawitz  and  Lossen  have  both  shown 
that  the  oedema  obtained  by  dry-cupping  is  no 
greater  in  haemophilics  than  it  is  in  normal 
individuals. 

So  far,  then,  there  is  substantial  agreement. 
When  w'e  seek  to  go  further,  and  to  inquire  just  which 
we  are  to  blame  of  the  various  elements  that  take 
part  in  regulating  the  coagulation  of  the  blood,  the 
problem  becomes  complicated. 

Theoretically,  the  delay  might  be  due  to : — 
(i)  Deficient  quantity  or  quality  of  the  fibrinogen  ; 
(2)  Deficiency  or  excess  of  calcium  salts  ;  (3)  De- 
ficient quantity  or  quality  of  the  thrombokinase  ; 


36  RESEARCHES    ON    BLOOD 

(4)  Deficient  quantity  or  quality  of  the  prothrombin  ; 

(5)  Excess  of  antithrombin. 

In  the  examination  of  these  factors  we  follow  the 
researches  of  Addis.  The  main  point  to  determine 
is  whether  the  delay  is  in  the  first  or  the  second  of 
the  two  reactions  involved, — that  is,  in  the  conversion 
of  prothrombin  into  thrombin,  or  in  the  conversion 
of  fibrinogen  into  fibrin.  It  proves  that  the  former 
is  at  fault  ;  the  latter  is  quite  normal.  Haemophihc 
fibrinogen  is  as  readily  clotted  by  normal  or  by 
hasmophilic  thrombin  as  is  normal  fibrinogen,  and 
normal  fibrinogen  is  easily  clotted  by  thrombin  from  a 
bleeder.  But  haemophilic  blood  must  stand  a  long 
time  before  prothrombin  is  converted  into  thrombin. 

Taking  up  the  points,  then,  in  order  : — 

1.  The  defect  is  not  in  the  fibrinogen,  because  it 
is  readily  clotted  if  isolated  and  treated  with  throm- 
bin. Moreover,  when  clot  does  at  last  form  during 
a  haemorrhage,  it  is  as  firm  and  abundant  as  in 
ordinary  blood. 

2.  The  defect  is  not  in  the  calcium  salts,  because 
analysis  shows  no  abnormality  in  quantity,  and  the 
addition  of  these  salts  to  drawn  haemophihc  blood, 
though  it  may  hasten  the  time  of  clotting,  does  not 
bring  it  to  normal. 

3.  The  defect  is  not  in  the  thromhokinase.  Here 
Sahli  joins  issue  with  Addis,  because  the  addition  of 
washed  leucocytes  to  haemophihc  blood  rapidly 
causes  it  to  clot.  These  may,  however,  bring  in 
prothrombin  as  well  as  thromhokinase,  and  Addis 
shows  that  solutions  of  thromhokinase,  derived  by 
crushing  up  testis  in  saline,  have  far  less  effect  on 


RESEARCHES    ON     BLOOD  87 

haemophilic  than  on  normal  blood  unless  very  concen- 
trated extracts  are  used.  Again,  there  is  just  as  much 
thrombokinase  in  the  serum  of  a  bleeder,  squeezed 
out  after  coagulation,  as  in  that  of  a  normal  person. 

4.  //  is  in  the  prothrombin  that  the  defect  lies.  A 
very  little  normal  plasma,  or  a  few  washed  corpuscles 
from  a  normal  person,  restore  the  coagulation  power 
forthwith. 

Addis  believes  that  he  has  directly  proved  the 
point  by  the  adoption  of  the  following  method  for 
isolating  the  prothrombin,  and  at  the  same  time  he 
has  established  that  in  the  haemorrhagic  diathesis  it  is 
deficient  not  in  quantity  but  only  in  character.  He 
prepared  a  solution  of  fibrinogen  from  normal  or 
hctmophilic  plasma  in  the  ordinary  way  by  precipi- 
tating it  b}^  passing  a  stream  of  carbon  dioxide  through 
plasma  kept  from  clotting  by  citrate  or  oxalate. 
Fibrinogen  so  obtained,  as  Mellanby  shows,  always 
carries  with  it  prothrombin,  and  in  the  presence  of 
calcium  salts  and  thrombokinase  would  liberate 
thrombin.  Addis,  however,  added  instead  a  trace  of 
thrombin,  which  clotted  the  fibrinogen  and  left  its 
prothrombin  in  solution.  When  a  trace  of  prothrombin 
so  obtained  from  a  normal  blood  was  added  to  hasmo- 
philic  blood,  this  promptly  coagulated.  (The  criticism 
would  of  course  be  that  there  was  some  unused 
thrombin  present  as  well,  too  much  having  been  added 
to  the  fibrinogen.) 

Thus,  the  exact  pathology  of  hai'mophilia  would  be, 
in  Addis's  opinion,  a  congenital  defect  in  the  con- 
stitution of  the  prothrombin,  whereby  it  yields 
thrombin  much  too  slowly.  Possibly  the  leucocytes 
are  ultimately  at  fault. 


38  RESEARCHES    ON    BLOOD 

The  practical  deduction  we  shall  see  later. 

5.  There  is  no  excess  of  antithromhin  in  the  plasma 
of  the  bleeder.  If  there  were,  the  addition  of  a  trace 
of  normal  blood  would  not  cause  haemophilic  blood 
to  clot  as  it  does,  because  any  thrombin  in  the  former 
would  be  overpowered  and  destroyed  b}'  the  anti- 
thromhin in  the  latter. 

To  sum  up,  the  secret  of  haemophilia  Ues  in  a 
defective  quahty  of  the  prothrombin,  such  that  it 
takes  much  longer  than  usual  to  develop  into 
thrombin.  No  evidence  is  yet  to  hand  to  show 
whether  the  haemorrhagic  tendencies  in  scurvy, 
purpura,  pernicious  anaemia,  and  occasionally  in 
jaundice  have  the  same  explanation. 

It  is  important  to  bear  in  mind  the  fact  that 
certain  cases  of  jaundice  may  ooze  to  death  by 
capillary  haemorrhage  after  operation  ;  most  of  us 
can  recollect  instances  of  this  calamity.  It  has  been 
recommended  to  give  drachm  doses  of  calcium 
chloride  for  three  days  before  the  operation,  but 
probably  a  more  useful  proceeding  would  be  to  take 
the  coagulation  time  by  means  of  a  Wright's  tube, 
and  to  refuse  to  operate  on  any  cases  showing  serious 
delay. 

It  will  be  gathered  that  unfortunately  the  under- 
lying causes  of  haemophilia  do  not  lend  themselves 
to  direct  remedy.  We  cannot,  except  by  one  drastic 
proceeding,  influence  the  quality  or  quantity  of  the 
more  complicated  and  specialized  fibrinoplastic 
elements  in  the  blood,  and  we  can  use  only  those 
means  which  in  a  general  way  are  understood  to 
increase  the  coagulability. 


RESEARCHES    ON    BLOOD  39 

Sometimes  the  ordinary  surgical  means  such  as 
rest,  pressure,  plugging,  or  adrenalin  may  be  success- 
ful. It  is  usually  advised  not  to  stitch  wounds, 
for  fear  of  bleeding  from  the  punctures,  but  if  these 
are  made  with  a  small,  round-bodied  needle,  the 
elasticity  of  the  skin  will  prevent  oozing.  Therefore, 
if  tight  stitching  would  obviously  bring  useful 
pressure  to  bear,  it  should  be  resorted  to,  but  only 
in  the  skin,  not  in  mucous  membranes. 

It  has  been  advised,  and  the  advice  is  physio- 
logically sound,  to  apply  normal  human  blood  to  the 
oozing  point.  Unhappily,  even  if  a  mass  of  clot  is 
formed  over  the  wound,  it  soon  gets  pushed  away  by 
the  collection  of  unclotted  blood  beneath  it.  For 
the  normal  arrest  of  haemorrhage  it  is  necessary  either 
that  clotting  should  take  place  inside  the  bleeding 
vessel  or  that  it  should  fill  the  wound  so  tightly  about 
this  vessel  as  to  present  a  complete  block  to  the  flow. 
It  is  often  impossible  to  get  the  remedy  near  enough 
to  the  actual  rent  in  the  arter}^  or  capillary  to  bring 
this  about,  and  the  shape  of  the  wound  may  not  lend 
itself  to  filling  up  tightly  with  firm  clot.  Nevertheless 
the  method  is  simple  and  painless,  and  has  some- 
times succeeded. 

Styptics  such  as  ferric  chloride,  tannin,  or  alum 
may  be  applied  to  the  wound,  but  they  are  painful 
and  lead  to  much  sloughing,  so  it  is  well  first  to 
give  a  brief  trial  to  fresh  normal  blood  apphed  by 
wool  pledgets,  and  to  Wright's  physiological  styptic 
(thrombokinase),  composed  of  one  part  of  minced 
thymus  in  ten  parts  of  normal  saline.  This  produces 
a  firm  clot,  but  does  not  act  as  quickly  as  the 
escharotic  styptics. 


40  RESEARCHES    ON    BLOOD 

IntemaU}^  Wright  gives  calcium  salts,  preferabh'' 
the  lactate,  but  admittedly  this  is  a  bow  drawn  at  a 
venture,  because  the  calcium  is  often  absorbed  very 
badly,  and  may  already  be  at  the  optimum  in  the 
blood.  The  first  difficulty  may  be  obviated  in  some 
patients  by  using  magnesium  lactate  or  carbonate. 
The  doses  of  any  of  these  drugs  should  be  60  grains 
for  adults,  and  15  grains  for  children,  at  once,  followed 
by  lo-grain  doses  three  times  a  da\^  for  three  days 
for  adults,  with  a  corresponding  reduction  for 
children.  Calcium  salts  reverse  their  effect  after 
three  days. 

To  the  same  authority  we  are  indebted  for  the 
suggestion  that  we  should  administer  carbon  dioxide 
gas,  either  from  a  Kipp's  apparatus  containing 
marble  and  h3'drochloric  acid,  or  from  a  cyHnder  of 
the  gas.  Venous  blood  is  much  more  coagulable 
than  arterial.     Dyspnoea  should  be  avoided. 

Weil  recommends  the  injection  of  horse-serum, 
conveniently  obtained  as  diphtheria  antitoxin.  It 
probably  increases  the  rate  of  blood-clotting,  but 
apparently  not  until  many  hours  have  passed,  and 
consequently  it  often  fails  in  practice. 

There  remains  one  last  resort  in  the  most  desperate 
cases,  and  no  patient  should  be  allowed  to  die  of 
hcemophilia  without  its  being  attempted.  We  have 
seen  that  there  is  only  one  way  to  restore  prompt 
coagulability  to  haemophiHc  blood,  and  that  is  to 
supply  normal  blood. 

Goodman  has  published  a  well- written,  almost 
dramatic  description  of  his  treatment  of  a  Jewish 
boy,  aged  two  and  a  half,  a  well-known  bleeder  and 


RESEARCHES    ON    BLOOD  41 

member  of  a  bleeder  family,  who  was  moribund  from 
haemorrhage  from  a  cut  mside  the  cheek,  which  had 
oozed  incessantly  for  two  days.  Pressure,  adrenalin, 
styptics,  calcium  salts,  and  horse-serum  (antitoxin) 
had  all  been  tried  in  vain,  and  finally  the  child  lay 
motionless  and  pallid,  scarcely  breathing,  with 
haemoglobin  down  to  12  per  cent,  and  haemorrhage 
continuing. 

Goodman  decided  to  inject  normal  human  blood. 
A  donor,  not  a  relative,  was  tested  by  Wassermann's 
test  for  syphilis,  and  declared  free.  Under  novocain 
anaesthesia  his  radial  artery  was  connected  by  an 
Elsberg  cannula  with  the  child's  femoral  vein. 
There  were  some  initial  difficulties  in  getting  a  good 
flow,  and  hot  cloths  had  to  be  applied  ;  finally  the 
basihc  vein  was  substituted  for  the  femoral  on  account 
of  differences  in  the  level  of  these  patients.  Trans- 
fusion was  continued  for  twenty-eight  minutes. 
During  this  time  colour  gradually  mounted  up  in 
the  cheeks  of  the  Httle  sufferer,  the  breathing  became 
audible  once  more,  the  almost  watery  blood  acquired 
its  normal  hue,  and  the  haemoglobin  rose  to  70  per 
cent.  Most  significant  of  all,  the  bleeding  was 
completely  and  permanently  arrested,  and  there  was 
no  haemorrhage  from  the  incisions. 

ANAPHYLAXIS. 
It  is  well  known  that  when  certain  proteins  are 
injected  into  an  animal's  blood-stream,  so  far  from 
antibodies  being  formed,  there  may  be  an  increased 
sensitiveness  developed,  so  that  a  second  injection 
months  or  years  afterwards  may  produce  severe  or 


42  RESEARCHES    ON    BLOOD 

even  fatal  symptoms.  A  few  cases  are  on  record  in 
which  second  injections  of  horse- serum  containing 
diphtheria  or  other  antitoxin  have  caused  most 
alarming  illness  or  death.  Now  that  so  many  men 
who  were  wounded  in  the  war  and  given  a  dose  of 
antitetanic  serum  are  about  in  the  community,  it  is 
possible  that  there  may  be  trouble  one  day  when 
one  of  them  is  given  diphtheria  antitoxin  or  some 
other  preparation  of  horse-serum  protein.  It  is 
also  well  known  that  if  the  second  dose  is  given 
\\ithin  a  week  this  sensitization  (anaphylaxis)  does 
not  occur. 

The  symptoms  in  severe  cases  are  due  to  intense 
swelling  of  the  mucosa  of  the  bronchi,  causing 
suffocation  and  conMilsions.  In  mild  cases  they 
resemble  those  of  ordinary  serum  sickness — an 
urticarial  or  measly  rash,  joint  pains,  and  the  like. 

Evidence  has  accumulated  that  anaphylaxis  may 
explain  some  other  conditions  besides  serum  poison- 
ing. It  occasionally  happens  after  tapping  or 
operating  on  a  hydatid  cyst  that  there  may  be 
violent  urticaria,  or  in  a  few  cases  fatal  suffocative 
symptoms  (intoxication  hydatique).  This  is  an 
anaphylactic  phenomenon. 

Some  cases  of  asthma  and  hay  fever  appear  to  be 
due  to  the  inhalation  of  a  foreign  protein  of  animal 
or  vegetable  origin  to  which  the  patient  is  super- 
sensitive. Sometimes  the  foreign  protein  is  con- 
veyed in  the  diet,  and  white  of  egg  would  seem  to 
be  the  commonest  offender.  In  yet  other  cases  it  is 
of  bacterial  origin.  A  careful  history  may  help  to 
detect  the  source  of  the  trouble,  and  if  the  skin  is 


RESEARCHES     OX     BLOOD  48 

scratched  and  a  solution  of  the  suspected  substance 
—grass  pollen,  egg-albumen,  milk,  or  whatever  it  is— 
painted  on  the  scariftcations,  there  will  be  swelling 
and  redness.  It  may  then  be  possible  to  avoid  the 
article,  or  to  obtain  an  acquired  immunity  by  starting 
\nth  exceedingly  minute  doses  (say  i  mgrm.  of  egg- 
albumen)  and  increasing  very  cautiously. 

Intractable  eczema  in  children  may  be  caused  in 
the  same  way.  The  testing  out  may  need  to  be 
quite  elaborate,  using  milk  protein,  fat  and  sugar 
separately,  egg-albumen,  and  watery  extracts  of 
various  food-stuffs  filtered,  precipitated  with  alcohol, 
washed,  and  appUed  in  powdered  form.  According 
to  W^iite,  in  two-thirds  of  the  cases  a  positive  result 
was  obtained  to  some  food-stuff  or  other. 

THE  THERAPEUTICS  OF  CALCIUM  SALTS. 
So  much  interest  has  lately  attached  to  this  subject 
that  brief  mention  only  will  be  called  for  of  the  uses 
to  which  calcium  salts  have  been  put.  It  has  long 
been  recognized  by  physiologists  that  they  are 
essential  to  the  continued  success  of  perfusion  fluids, 
and  now  we  know  that  they  control  the  coagulation 
and  viscosity  of  the  blood,  and  probably  the  functions 
of  the  ovary  and  parathyroid  glands  also. 

Remarkable  results  have  been  obtained  in  many 
cases  by  giving  calcium  lactate  in  15-gr.  doses  thrice  a 
day,  for  three  days  only,  in  the  following  conditions  : 

Transient  or  functional  albuminuria. 

•  Lymphatic '    headache    frequently   recurnng    m 

anaemic  young  women. 
Some  urticarial  eruptions. 


44  RESEARCHES    ON    BLOOD 

Chilblains.  In  this  common  complaint  it  may 
work  like  a  charm. 

All  varieties  of  tetany. 

The  symptoms  of  the  menopause  are  sometimes 
greatly  relieved  by  calcium  lactate. 

In  all  the  above,  however,  there  is  one  constantly 
recurring  source  of  fallacy.  The  power  to  absorb 
calcium  from  the  bowel  varies  much  in  different 
people,  and  some  observers  record  negative  results 
after  giving  the  drug.  Magnesium  salts  will  some- 
times be  more  effectual  if  calcium  fails  to  get  into 

the  blood. 

REFERENCES. 
Keith,    Rowntree,   and    Geraghty. — Archiv.    Int.    Med., 

1915,  p.  547. 
Robertson  and  Bock. — Jour,  of  Exper.  Med.,  1919,  Feb., 

PP-  139.  154- 
Kerr,  Hurwitz,  and  Whipple. — Amer.  Jour,  of  Phys.,  vol. 

xlvii,   191S,  pp.  356,  370,  379. 
Rendle  Short. — Med.  Anmtal,  1919,  p.  9. 
AsHBY. — Jour,  of  Exper.  Med.,  1919,  March,  p.  267. 
Robertson  and  Rous. — Jour,  of  Exper.  Med.,   191 7,  xxv, 

pp.  651,  665. 
Pearce,   Krumbhaar,  Frazier. — The  Spleen  and  Ancsmia, 

1917. 
Whipple  and  Hooper. — Anier.  Jour,   of  Phys.,   191 7,   xlii, 

P,  544- 
Ledingham  and  Bedson. — Lancet,   1915,  i,  p.  309. 
Lee  and  Robertson. — Jour.  Med.  Research,  1916,  xxiii,  p. 

323- 
Lee  and  Minot. — Cleveland  Med.  Jour.,  xvi,  191 7,  p.  65. 
Mellanby. — Jour,  of  Physiology,  1909,  p.  28. 
Sir  Almroth  Wright. — Allbutt's  System  of  Medicine,  1909, 

vol.  V,  p.  918. 
Addis. — Quart.  Jour,  of  Medicine,    1910,   Oct.,   p.    14  ;    Brit. 

Med,  Jour.,  1910.  ii,  p.  1422. 
Goodman. — Annals  of  Sur^.,  1910,  Oct.,  p.  457. 
White. — Boston  Med.  and  Surg.  Jour.,  191S,  i,  p.  5- 


45 


CHAPTER    HI. 

THE     HEART. 

By  Carey  F.  Coombs,  M.D.,  F.R.C.P.  Lend.,  Assistant 
Physician^  Bristol  General  Hospital  ;   and 

C.  E.  K.  IlERAPATH,  M.C..  M.D.,  B.S.,  M.R.C.S.,  L.R.C.P., 

Medical  Registrar,  Bristol  Royal  Infirmary. 

DEVELOPMENT    AND  STRUCTURE    OF     THE    HEART- — -MODES     OF 

EXAMINATION       OF       THE     HEART  HEART    RHYTHMS  

PROPERTIES     OF       CARDIAC       MUSCLE   —   THE       NERVOUS 
SYSTEM    OF   THE  HEART CARDIAC    IRREGULARITIES. 


A 


T  the  beginning  of  the  third  week  of  foetal 
life  the  heart  consists  of  a  straight  muscular 
tube,  demarcated  into  four  parts  :  (i)  The  sinus 
venosus ;  (2)  The  primitive  auricle ;  (3)  The 
primitive  ventricle ;  (4)  The  bulbus  cordis.  The 
beat  begins  in  the  sinus  venosus,  and  is  carried  on  by 
a  peristaltic  wave  through  the  various  chambers  ot 
the  heart  in  the  order  given  above.  A  little  later  the 
tube  becomes  bent  upon  itself,  one  bend  occurring 
at  the  junction  of  auricle  and  ventricle  ;  the  other 
involves  the  ventricular  portion  of  the  tube,  which 
assumes  a  v  form.  As  a  result  of  these  bends  the 
auricle  takes  up  a  position  dorsal  to  the  ventricle  ; 
the  shorter  curvature  of  the  ventricular  bend  becomes 
absorbed,  forming  one  chamber.  At  this  time  septa 
appear  which  divide  the  primitive  auricle  and 
ventricle  into  two,  and  the  right  and  left  auricles 
grow  out  from  the  dorsal  portion  of  the  primitive 


46  THE    HEART 

auricle,  while  the  right  and  left  ventricles  grow  out 
from  the  ventral  and  lateral  portions  of  the  primitive 
ventricle.  The  sinus  venosus  gradually  comes  to  lie 
in  the  dorsal  wall  of  the  right  part  of  the  primitive 
auricle,  and  when  the  right  auricle  grows  out  it  takes 
the  sinus  venosus  with  it,  so  that  it  comes  to  lie  in  the 
wall  of  the  right  auricle.  The  balbus  cordis  becomes 
incorporated  chiefly  in  the  left  ventricle. 

The  auricular  canal,  which  is  the  connection 
between  the  primitive  auricle  and  ventricle,  becomes 
surrounded  by  an  upgrowth  of  the  base  of  the 
primitive  ventricle,  and  very  little  of  it  remains  in 
the  adult  heart ;  but  part  is  carried  down  in  the 
inter  auricular  septum. 

The  embryological  heart  muscle  has  the  property  of 
conducting  the  stimulus  from  the  sinus  venosus  to  the 
bulbus  cordis,  and  a  remnant  of  this  muscular  tube 
continues  to  act  as  the  conducting  path  in  the  adult 
heart,  so  that  to  understand  this  it  is  necessary  to 
trace  this  path  as  it  appears  in  the  adult  heart.  The 
sinus  venosus  has  been  seen  to  move  across  and  to 
lie  eventually  in  the  wall  of  the  right  auricle,  its 
structure  lying  chiefly  between  the  superior  and 
inferior  venae  cavae.  From  here  the  path  runs  down 
the  auricular  canal,  of  which  the  interauricular 
septum  is  the  chief  remains,  though  part  is  in- 
corporated in  the  wall  of  the  right  and  left  auricles. 

The  ventricles  are  chiefly  new  structures,  being 
formed  as  evaginations  from  the  primitive  ventricle, 
the  remains  of  which  are  chiefly  in  the  interven- 
tricular septum  which  grows  from  the  apex  upwards 
and  takes  most  of  the  embryological  ventricle  with  it. 


THE     HEART  47 

If  we  now  examine  the  recent  histolopjical  work 
on  the  conduction  path,  we  find  that  it  agrees  with 
what  has  been  shown  should  be  its  path  from  the 
morphological  aspect. 

The  place  of  origin  of  the  heart-beat  has  been 
proved  to  lie  at  a  point  in  the  sulcus  terminale  below 
the  junction  of  the  superior  vena  cava  and  the  right 
auricular  appendix,  and  a  patch  of  specialized  tissue 
is  found  in  this  position  which  is  known  as  the  sinu- 
auricular  node. 

Another  larger  node  of  similar  tissue  is  found  in 
the  posterior  part  of  the  interauricular  septum  below 
and  to  the  right  of  the  coronary  sinus.  From  this  a 
bundle  of  pale  muscular  fibres  similar  to  Purkinje 
fibres  passes  forwards  and  downwards  to  the  inter- 
ventricular septum,  where  it  divides  into  right 
and  left  branches.  Each  of  these  passes  down 
beneath  the  endocardium  of  the  septum  of  its  respec- 
tive ventricle,  and  divides  into  branches  which  are 
distributed  to  the  papillary  muscles  and  the  mural 
muscles  of  the  ventricles. 

Thus  a  complete  path  has  been  traced  from  the 
sinu-auricular  node  to  the  ventricles,  except  the 
part  between  the  sinu-auricular  node  and  the 
auriculoventricular  node.  The  stimulus  is  supposed 
to  cover  this  interval  by  passing  through  the 
auric  alar  muscle  in  all  directions.  But  work  on 
dogs  by  electrical  methods  suggests  that  the  stimulus 
reaches  the  auriculoventricular  node  before  the 
auricular  muscle.  Again,  under  certain  conditions 
a  reversed  rhythm  may  take  place,  the  sequence 
of  beat  being  ventricle,  auricle,    and  it   has   been 


48  THE    HEART 

shown  that  in  this  case  the  stimulus  reaches  the 
sinu-auricular  node  before  the  auricular  muscle. 
These  two  data  point  to  the  existence  of  some 
direct  path  between  sinu-auricular  and  auriculo- 
ventricular  nodes  which  does  not  lie  through  the 
auricular  muscle,  but  so  far  this  path  has  not  been 
certainty  identified  anatomically. 

In  birds  there  is  no  auriculoventricular  bundle  and 
node  such  as  has  been  described  above,  but  the 
stimulus  is  conducted  bj^  a  muscular  connection 
which  lies  in  the  posterior  part  of  the  auriculoven- 
tricular groove  in  the  region  of  the  left  superior  vena 
cava.  A  similar  path  has  been  described  in  this 
position  in  man,  and  also  another  lying  in  the  right 
auricular  wall  almost  on  the  extreme  right  lateral 
aspect  of  the  heart  slightly  towards  the  posterior 
surface.  So  far  as  is  known,  these  paths  do  not 
convey  stimuli  in  man. 

MODES  OF  EXAMINATION  OF  THE  HEART. 

]\Iuch  of  the  recent  physiological  work  on  the 
heart  has  been  stimulated  by  clinicians  who  by 
means  of  special  instruments,  the  polygraph  and 
the  electrocardiograph,  have  classified  the  irregulari- 
ties of  the  heart. 

The  polygraph  is  an  instrument  bj'  means  of  which 
simultaneous  records  of  the  venous  and  arterial 
pulses  are  obtained,  with  the  addition  of  a  time- 
marker,  so  that  the  actual  time-intervals  of  the 
various  events  in  the  cardiac  cycle  may  be  worked 

out. 
The  venous  pulse  is  obtained  from  the  jugular 


THE     HEART 


Ay\ 


49 


bulb  lying  just  above  the  clavicle,  i  to  ij  inches 
external  to  the  sternoclavicular  synchondrosis.  The 
ri,<ht  side  is  usually  preferable  to  the  left.  It  nor- 
mally consists  of  three  waves  of  positive  pressure, 
«,  c,  and  V,  and  two  waves  of  negative  pressure, 
X  and  y  (see  dia^rayu). 

The  a  wave  is  caused  by  the  auricular  contraction. 
As  soon  as  this  is  over  there  is  a  fall,  x,  due  to  the 
blood  rushing  into  the  dilating  auricle ;  this  is  inter- 
rupted by  c,  a  wave  caused  by  the  sudden  systole  of 


ssec. 


FtR 


the  ventricle  closing  the  auriculoventricular  valves 
with  a  snap  and  communicating  a  shock  to  the  auricle 
and  jugular  vein  ;  it  occurs  at  the  commencement  of 
systole,  and  marks  the  onset  of  systole  in  the  venous 
pulse. 

During  ventricular  systole  the  auricle  fills  and  the 
pressure  in  the  jugular  vein  rises,  causing  the  v  wave. 
As  soon  as  systole  is  ended,  the  auriculoventricular 
valves  open  and  a  sudden  drop  occurs  (v  in  diagram), 
as  the  blood  rushes  into  the  ventricle.     Consequently 


50  THE    HEART 

the  summit  of  v  or  the  commencement  of  y  marks 
the  end  of  ventricular  systole.  The  v  wave  is  com- 
monly notched  or  in  two  portions.     This  division  of 

V  marks  the  closing  of  the  arterial  valves. 

A  tracing  of  the  radial  pulse  is  taken  at  the  same 
time  to  serve  as  a  record  of  the  ventricular  action. 
It  should  be  noted  that  the  radial  pulse  occurs  ,V 
second  after  the  carotid  pulse.  Let  us  now  discuss 
how  a  tracing  is  read  and  what  evidence  may  be 
obtained  from  it. 

As  soon  as  the  machine  is  stopped,  each  pen  should 
be  moved  so  as  to  mark  on  the  paper  the  point  at 
which  each  lever  stopped.  These  marks  are  called 
ordinates,  and  are  important  for  measuring.  With 
a  pair  of  calipers  the  distance  between  the  ordinate 
and  the  commencement  of  a  radial  upstroke  is 
measured.  By  means  of  the  time-marker  ^\j  second 
is  added  on  to  this  distance  to  allow  for  the  earlier 
onset  of  the  pulse  in  the  neck.  If  one  end  of  the 
calipers  is  now  placed  on  the  venous-pulse  ordinate, 
the  other  will  mark  the  onset  of  ventricular  systole 
in  the  venous  pulse,  and  a  wave  will  be  found  com- 
mencing its  upstroke  at  this  point.  This  is  the  c 
wave.  Having  marked  this  on  the  tracing,  a  wave 
wiU  be  found  about  i  second  previous  to  this,  and 
this  will  be  the  a  wave.  Shortly  after  the  c  wave 
will  be  found  the  v  wave,  and  the  summit  of  v  will  be 
found  to  synchronize  with  the  cUcrotic  notch  in  the 
radial ;  in  other  words,  the  distance  from  c  to  end  of 

V  is  the  length  of  the  ventricular  systole.  The  com- 
mencement  of  v  is  not  a  fixed  point,  as  it  depends  on 
the   venous  pressure  ;   the  higher  the  pressure  the 


THK     ilKAKT  51 

earlier  it  will  appear,  as  the  auricle  will  Jill  more 
quickly.  In  cases  where  the  a  wave  is  (l<jubtful, 
owing  to  diastole  being  very  short,  as  in  rapidly- 
beating  hearts,  the  fixation  of  the  summit  of  ?-  will 
often  help  in  determining  which  is  the  a  wave  and 
which  the  v. 

The  interval  between  the  commencement  of  a  and 
c  is  normally  1  second,  and  is  used  as  a  measure- 
ment of  the  time  taken  for  the  stimulus  to  reach  the 
ventricle  from  the  sinu-auricular  node.  Any  increase 
of  the  d-c  interval,  as  it  is  called,  is  looked  upon  as 
an  indication  of  dela^^  in  the  conductivity  of  the 
auriculoventricular  bundle. 

In  slow-acting  hearts  a  fourth  wave  {h  in  diagram) 
may  be  sometimes  found ;  this  occurs  in  early 
diastole,  and  is  accompanied  by  the  third  heart 
sound.  It  is  caused  by  the  sudden  rush  of  blood 
into  the  dilating  ventricle  floating  up  the  cusps  of 
the  auriculoventricular  valves  and  momentarily 
closing  them. 

The  venous  pulse  is  thus  normally  composed  of 
three  waves  to  every  systole  of  the  ventricle,  and  this 
is  known  as  the  auricular  type  of  venous  pulse. 

In  some  conditions  the  a  wave  may  entirely  dis- 
appear, so  that  the  venous  pulse  consists  of  two 
waves,  the  c  and  v,  and  these  may  again  be  fused 
into  one  broad  wave.  These  waves  fall  entirely  in 
the  ventricular  systole ;  hence  it  is  called  the  ven- 
tricular venous  pulse. 

The  ventricular  type  of  venous  pulse  occurs  in 
the  following  conditions  : — 

I.  In   rapidly-beating  hearts   where   the   a   wave 


52  THE     HEART 

falls  on  the  preceding  c  or  v  waves.  If  conduction 
be  impaired  and  the  a-c  interval  long,  it  is  easy  for 
the  a  wave  to  occur  coincidently  with  the  preceding 
c  wave. 

2.  In  conditions  of  marked  increase  in  venous 
pressure  in  the  right  auricle  and  great  veins — the 
polygraph  may  fail  to  record  the  a  wave. 

3.  In  atrioventricular  rhythm  where  the  auricle 
and  ventricle  are  beating  synchronously. 

4.  In  auricular  hbrillation,  where  the  auricle  no 
longer  contracts  normally.  As  will  be  seen  later, 
the  heart  is  completely  irregular,  and  small  irregular 
waves  ma}^  be  sometimes  detected  in  the  venous 
pulse  due  to  the  fibrillary  contractions  of  the  auricle. 

The  electrocardiograph  is  a  more  exact  method  of 
registering  the  action  of  the  chambers  of  the  heart, 
and  is  of  use  in  analyzing  conditions  which  are  not 
clear  in  polygraph ic  tracings.  Great  strides  have 
been  made  in  experimental  physiology  and  in  dia- 
gnosing abnormal  rhythms  in  man  by  means  of  its 
use. 

Cardiac  muscle,  like  all  muscle,  gives  rise  on  con- 
traction to  differences  in  electrical  potential,  and  as 
a  wave  of  contraction  passes  through  the  heart,  a 
wave  of  electro-negati\dty  passes  with  it.  If  the 
base  and  apex  of  a  heart  are  joined  up  to  a  string 
galvanometer,  minute  currents  pass  through  it  and 
cause  certain  deflections  of  the  string. 

It  is  found  that  these  currents  may  also  be  led  off 
from  the  limbs  of  patients  :  thus  we  may  get  tracings 
from  right  and  left  arms,  right  arm  and  left  leg,  and 


THK     UKAHT  53 

left  arm  and  left  leg.  These  are  respectively  known 
as  leads  I,  II.  and  III.  Lead  II  is  the  one  most 
commonly  used,  but  in  cases  of  difficulty  help  may 
be  obtained  from  all  three. 

A  string  galvanometer  works  on  the  following 
principle.  If  an  electrical  conductor  in  the  shape  of 
a  line  thread  be  placed  between  the  magnetic  poles 
of  a  powerful  electromagnet,  it  is  found  that,  should 
minute  currents  be  passed  through  the  fibre,  a 
deflection  of  the  fibre  occurs  relative  to  the  strength 
of  the  current.  Also  it  is  found  that  currents  passing 
in  one  direction  cause  a  deflection  to  one  side,  while 
reversing  the  current  causes  a  deflection  to  the 
opposite  side.  The  fibres  are  made  of  very  fine 
silvered  quartz  or  fine-drawn  platinum. 

In  the  Cambridge  pattern  the  poles  of  the  magnet 
are  drilled  through  the  centre  and  a  telescope  is 
placed  in  position,  so  that  if  the  light  from  an  arc 
lamp  be  thrown  through  the  telescope,  the  shadow 
of  the  string  may  be  focussed  on  a  photographic 
apparatus  with  a  moving  plate  or  paper,  and  any 
deflections  of  the  string  will  be  reproduced.  A  time- 
marker  is  arranged  to  mark  4  or  yV  second  on  the 
photograph,  and  in  this  way  an  accurate  timing  of 
any  movements  of  the  string  may  be  determined. 

In  a  German-pattern  instrument  the  principle  is 
slightly  different  :  the  conducting  fibre  is  passed  up 
and  down  between  the  poles  of  the  magnet,  and  a 
very  small  mirror  is  cemented  on  to  the  strings. 
Thus  the  cun-ent  passes  up  one  string  and  down  the 
other,  causing  a  deflection  in  one  direction  in  one 
string  and  the  opposite  deflection  in  the  other  ;  this 


54 


THE    HEART 


causes  a  deflection  of  the  mirror,  and,  if  a  powerful 
light  be  thrown  on  the  mirror,  the  movements  of  the 
reflected  beam  of  light  may  be  photographed  on 
moving  sensitized  paper.  This  apparatus  has  four 
strings  placed  side  by  side,  and,  by  means  of  an 
electric  microphone  which  transforms  sounds  such  as 
the  heart  sounds,  or  movements  of  columns  of  air 
such  as  we  get  from  records  of  pulses,  into  electric 
currents,  simultaneous  records  of  the  heart  currents, 
heart  sounds,  and  arterial  and  venous  pulses  may 
be  taken. 

Simultaneous  tracings  have  been  taken  with  the 
former  method,  but  it  requires  a  separate  light  and 
galvanometer  for  each  record. 

An  electrocardiogram  taken  with  lead  II  is  shown 
in  the  accompanying  figure. 


s  sec. 


We  see  that  there  are  waves  marked  P,  Q,  R,  S, 
and  T.  P  is  caused  by  the  auricular  systole,  and  is 
in  an  upward  direction.  Q.  R.  S,  and  T  are  caused 
by  ventricular  systole.  Q  and  S  are  in  a  downward 
direction,  but  are  very  variable.  Q  is  hardly  shown 
in  the  figure  ;  S  is  larger  than  usual,  but  it  may  be 
absent. 


THK     UK  ART  55 

R  is  the  largest  deflection,  and  is  very  cjuickly 
over.  T  is  a  small  slow  deflection,  and  marks  the 
end  of  systole. 

This  form  of  electrocardiogram  occurs  when  the 
contraction  of  the  chambers  of  the  heart  takes  place 
in  the  normal  sequence  and  the  conduction  of  the 
excitation  wave  follows  the  normal  course.  Varia- 
tion in  either  of  these  two  points  causes  changes  in 
the  forms  of  the  waves :  thus,  if  an  auricular  con- 
traction commences  in  the  base  instead  of  in  the 
upper  part,  the  p  wave  is  inverted. 

The  ventricular  complex  is  normal  so  long  as  the 
impulse  reaches  the  ventricular  muscle  by  means  of 
the  auriculoventricular  bundle  ;  but  if  a  contraction 
starts  in  the  ventricular  muscle,  an  abnormal  com- 
plex appears  which  varies  according  to  the  place  of 
origin  of  the  abnormal  beat.  In  the  same  way,  if 
one  of  the  branches  of  the  auriculoventricular 
bundle  be  blocked,  the  stimulus  reaches  the  muscle 
of  that  ventricle  by  some  abnormal  path,  and  a 
variation  in  the  complex  is  produced. 

For  the  various  types  of  complexes  associated 
with  abnormal  beats,  the  reader  is  referred  to  text- 
books. 

The  P-R  interv^al,  corresponding  to  the  a  c 
interval  of  polygraphic  tracings,  may  be  very 
accurately  measured,  and  is  found  to  vary  in  normal 
pei-sons  from  o*i2  to  0'i8  sec. 

Most  of  this  time  is  taken  for  the  stimulus  to 
traverse  the  auriculoventricular  node.  Any  increase 
of  this  interval  means  delay  in  conductivity  in  some 
part  of  the  auriculoventricular  bundle. 


56  THE     HEART 

HEART  RHYTHMS. 
It  has  been  stated  that  the  normal  rhythm  of 
the  heart  starts  in  the  sinu-auricular  node,  which 
•has  been  termed  the  '  pace-maker  '  of  the  heart. 
The  proof  of  this  Hes  in  experimental  work  on 
animals.  The  region  of  the  node  is  the  first  point 
in  the  heart  to  become  electro-negative.  Electro- 
cardiographic ally  the  complex  of  auricular  activity 
in  normal  beats  is  identical  with  the  complex 
gbtained  in  a  beat  originated  in  this  region  by  a 
mechanical  stimulus,  and  a  similar  complex  can  be 
obtained  from  no  other  portion  of  the  auricles. 

In  a  normally- beating  heart,  cooling  the  region  of 
the  sinu-auricular  node  slows  the  rate  of  beat,  warm- 
ing it  accelerates  it,  and  this  is  the  only  part  of  the 
heart  which  reacts  in  this  way.  If,  however,  the 
sinu-auricular  node  be  cooled  with  ice-cold  water,  a 
different  rhythm  starts,  which  has  been  proved  by 
the  electrocardiograph  to  originate  in  the  auriculo- 
ventricular  node,  and  called  the  atrioventricular 
rhythm . 

In  dogs  the  auriculo ventricular  node  has  an  up- 
ward prolongation  which  extends  round  the  coronary 
sinus,  and  is  di\aded  into  an  auricular  portion  and  a 
ventricular  portion.  The  former  is  the  prolongation 
in  the  neighbourhood  of  the  coronary  sinus,  the 
latter  further  forward.  Each  of  these  portions  has 
been  found  capable  of  originating  a  rhythm  of  its 
own.  It  is  known  that  a  rhythm  can  originate  from 
the  auriculoventricular  node  in  man,  but  no  auricular 
portion  of  the  node  has  as  yet  been  described. 
Other   methods,   such    as   excising,   clamping,    or 


THE     HKART  57 

poisoning  the  sinu-auricular  node,  have  been  found 
efficacious  in  producing  an  atrioventricular  riiythm. 
If  the  auriculo ventricular  node  be  put  out  of  action, 
a  rhythm  starts  in  the    Purkinje  fibres   below  the 
node,  forming  what  is  known  as  the  idioventricular 
rhythm.     So  that  there  are  three  main  pace-makers 
of  the  heart,  which  may  replace  each  other  if  necessity 
arises,  each  successive  rhythm  in  the  order  described 
being  of  a  slower  rate  than  the  previous  one.     This 
arrangement  prevents  the  rhythm  in  action  being 
interfered  with  by  a  rhythm  of  a  lower  order  ;  but  if, 
owing  to  disease,  a  pace-maker  of  a  lower  rhythm 
becomes  more  irritable  than  that  of  a  higher  rhythm, 
the  lower  rhythm  may  assert  itself  and  replace  that 
of   the   higher.     In   the   same  way,  any   particular 
portion  of  the  musculature  of  the  heart  may  have 
its  irritability  so  increased  that  a  rhythm  may  start, 
having  its  origin  in  this  irritated  focus.     In  slow- 
acting  hearts  with  a  sinus  rhythm  we  do  occasionally 
see  an  escaped  beat  or  a  short  series  of  beats  belong- 
ing to  a  lower  rhythm  appearing  in  a  tracing. 

PROPERTIES     OF     CARDIAC     MUSCLE. 

Heart  muscle  carries  on  its  work  by  means  of  five 
special  functions.  These  are :  (i)  Stimulus  pro- 
duction ;  (2)  Conductivity ;  (3)  Excitability ;  (4) 
Contractility  ;    (5)  Tonicity. 

Ordinary  muscles  remain  immobile  till  some  nerve- 
cell  discharges  a  stimulus  which  is  conducted  by  a 
nerve-fibre  to  the  muscle,  which  then  responds  to 
the  stimulus  with  a  contraction. 


58  THK     HEART 

Heart  muscle,  if  suitably  nourished,  will  contract 
rhythmically  when  isolated  from  the  body  and  all 
its  nervous  connections  have  been  cut  ;  therefore  it 
is  certain  that  it  receives  its  stimulus  from  within. 
We  know  that  the  stimulus  commences  at  the  sinu- 
auricular  node.  If  this  structure  be  minutely 
studied,  we  find  that,  in  the  words  of  its  discoverer, 
"  it  consists  of  pale  cardiac  muscle  fibres  with  which 
the  nerves  appear  to  become  actually  continuous. 
This  tissue,  apparently  intermediate  in  nature 
between  muscle  and  nerve,  is  characteristic  of  the 
sinu-auricular  node ".  It  therefore  appears  that 
these  modified  muscle-cells  have,  during  develop- 
ment, taken  to  themselves  one  of  the  properties  of 
nerve-cells,  namely  the  originating  of  impulses.  But 
it  differs  from  an  ordinary  nerve-cell  inasmuch  as, 
instead  of  sending  out  a  rhythmic  series  of  stimuli 
such  as  causes  a  tetanus  in  an  ordinary  muscle  per- 
formmg  voluntary  movement,  it  originates  one 
stimulus  causing  one  contraction. 

In  the  same  way  the  muscle  of  the  auriculo- 
ventricular  bundle  has  developed  the  property  of 
conducting  an  impulse  as  nerve -fibres  do.  The  rate 
of  conduction  has  been  estimated  at  about  5  metres 
per  second,  which  is  much  nearer  the  rate  of  con- 
duction by  muscle  than  nerve,  nervous  impulses 
being  conducted  more  quickly. 

Excitability  and  contractility  are  properties  of  all 
muscles,  and  are  very  intimately  connected ;  the 
former  consists  of  the  power  to  receive  a  stimulus, 
and  the  latter  the  power  of  contraction  on  its 
receipt.     The  latent  period  between  excitation  and 


TlfK     IIKAKT  59 

the  comnicnccniont  of  contraction  is  about  o'ooi  sec. 
in  both  skeletal  and  cardiac  muscle. 

It  used  to  be  thought  tliat  heart  musck-  ditfered 
from  skeletal  in  that  submaximal  contractions  could 
be  obtained  in  the  latter  but  not  in  the  former. 
But  these  submaximal  contractions  are  in  reality 
maximal  contractions  of  some  of  the  muscle  fibres, 
while  a  stronger  stimulus  causes  contraction  of  mcjre 
hbres,  and  so  on  up  to  the  maximal  contraction. 

This  practical  response  is  probably  impossible  in 
cardiac  muscle.  The  interlacing  of  cardiac  fibres 
and  the  wide  ramification  of  the  Purkinje  system  of 
conduction  fibres  ensure  that  contraction  is  carried 
out  by  every  fibre  in  the  cardiac  muscle. 

These  two  kinds  of  muscle  also  differ  markedly  as 
to  their  refractory  period — the  time  after  a  con- 
traction during  which  the  muscle  is  unable  to  respond 
to  another  stimulus.  In  skeletal  muscle  this  is  very 
short,  about  o'ooi5  sec,  whereas  in  cardiac  muscle 
it  is  about  0'4  sec.  It  is  of  course  owing  to  this 
property  that  tetanization  of  cardiac  muscle  is  im- 
possible. 

Tonicity. — ^The  tone  of  muscles  may  be  defined  as 
the  tension  in  its  fibres  while  relaxed.  No  muscle 
relaxes  to  its  utmost  extent,  but  is  kept  in  a  state  of 
partial  contraction  or  tension.  The  tone  of  skeletal 
muscle  is  kept  up  by  means  of  a  reflex  nervous  path 
having  a  centre  in  the  spinal  cord,  and  it  is  controlled 
by  the  central  nervous  system.  Any  break  in  this 
reflex  arc  causes  loss  of  tone  and  complete  relaxa- 
tion of  the  fibres  of  the  muscle  concerned. 

In  cardiac  muscle  this  is  not  the  case,  for  the 


60  THE    HEART 

perfused  heart  beating  in  the  laboratory  retains  its 
tone.  It  will  be  seen  later  that  the  nerves  to  the 
heart  from  the  central  nervous  system  have  some 
influence  on  tone,  but  the  chief  function  of  tonicity 
lies  within  the  heart.  It  appears  that  the  character 
of  the  blood-supply  has  a  great  deal  to  do  \\ith  it, 
inasmuch  as  it  has  been  proved  experimentally  that 
the  volume  of  the  perfused  heart  becomes  smaller 
if  ,the  calcium  salts  be  increased,  while  it  becomes 
larger  if  the  potassium  salts  are  increased,  in  the 
perfusing  fluid.  Thus,  calcium  seems  to  increase 
tonicity,  potassium  to  decrease  it.  An  excess  of 
carbon  dioxide  in  the  blood  also  decreases  tonicity. 
The  degree  of  tone  determines  the  size  of  the 
ventricles  and  therefore  the  output  of  blood ;  in  fact, 
the  amount  of  blood  thrown  out  at  each  ventricular 
systole  is  the  mean  between  the  venous  pressure  and 
the  tone  of  the  muscle.  Loss  of  tone  is  a  determining 
factor  in  dilatation  of  the  heart. 

THE     NERVOUS  SYSTEM     OF     THE     HEART. 

Although  the  heart  can  beat  normally  under  suit- 
able conditions  when  removed  from  the  body,  in  life 
it  is  to  a  great  extent  controlled  by  the  central 
nervous  system.  The  medulla,  from  which  all  the 
vital  functions  of  the  body  are  controlled,  is  the 
home  of  cardiac  control.  Here  are  situated  the  vagus 
nuclei,  both  motor  and  sensoiy,  and  intimately  con- 
nected with  it  is  the  vasomotor  centre.  Stimuli  from 
the  heart,  great  vessels,  and  all  parts  of  the  body, 
are  continually  arriving  there  by  means  of  the 
afferent  fibres  of  the  sensory  nerves,  and  as  a  result 


TUK     HKART  6i 

of  these  messages  the  heart  is  slowed,  accelerated, 
etc.  The  efferent  nerves  controlling  the  heart  are 
the  vagi  and  the  sympathetic. 

The  impulses  reaching  the  heart  from  the  vai^us 
are  inhibitory,  causing  :  (i)  Slowing  or  stopping  of 
the  heart-beats  ;  (2)  Lowering  of  conductivity  or 
contractility  ;  (3)  Alterations  in  tonicity.  It  has 
been  shown  in  animals,  and  to  a  certain  extent  in 
man,  that  the  vagi  on  the  two  sides  differ  in  their 
action.  The  right  vagus  appears  to  act  mainly  on 
the  pace-maker  of  the  heart — the  sinu-auricular 
node — thereby  slowing  or  temporarily  stopping  the 
heart.  The  left  vagus  acts  more  on  the  auriculo- 
ventricular  node,  producing  delay  in  the  a-c  interval, 
or  even  heart-block,  partial  or  complete.  It  is 
thought  by  many  that  stimulation  of  the  vagus  may 
cause  a  weakening  of  the  contractions,  but  it  is  a 
difficult  matter  to  determine,  as  lengthening  of 
diastole  tends  to  increase  the  contractile  power  of 
the  heart  muscle. 

In  hearts  of  dogs  in  which,  by  cooling  the  sinu- 
auricular  node,  a-v  rhythm  has  been  obtained,  this 
rhythm  is  markedly  slowed  by  stimulation  of  the 
vagus,  but  the  idioventricular  rhythm  is  not 
affected. 

The  tone  of  the  heart  has  repeatedly  been  shown 
to  be  affected  by  stimulation  of  the  vagus,  though 
the  results  are  somewhat  contradictory  ;  sometimes 
the  tone  is  increased,  at  others  it  has  been  depressed. 
Changes  of  tone  from  drugs  which  have  been  proved 
to  occur  by  means  of  the  vagi,  are  prevented  by 
atropine,  which  paralyzes  the  vagi. 


€2  THE    HEART 

The  sympathetic  fibres  are  supplied  from  the  rami 
communicantes  arising  from  the  upper  dorsal  and 
possibly  the  lower  cervical  nerves.  They  are  carried 
to  the  heart  by  means  of  branches  from  the  cervical 
and  stellate  ganglia.  Their  action  is  the  direct 
opposite  of  the  vagi ;  their  stimuli  accelerate  and 
augment  the  beat  of  the  heart  and  increase  con* 
ductivity.  Some  workers  have  also  been  able  to 
show  differences  in  action  between  the  right  and  left 
accelerator  fibres,  the  right  being  concerned  mostly 
with  the  sinu-auricular  node  and  causing  acceleration 
of  sinus  rhythm,  while  the  left  may  produce  a-v 
rhythm,  with  or  without  tachycardia.  The  experi- 
ments of  course  only  refer  to  animals,  though  it  is 
likely  that  the  same  effects  may  occur  in  man. 

The  rate  of  the  heart-beat  appears  to  depend  on 
the  balance  of  vagal  and  sympathetic  action.  Each 
is  continually  in  activity,  and  factors  which  increase 
the  one  usually  depress  the  other  ;  but  in  certain 
marked  alteration  in  rhythms,  one  function  may  be 
completely  inhibited, .  allowing  full  control  to  the 
other. 

The  afferent  system  of  sensory  fibres  passes  up  to 
the  medulla  in  the  vagus.  It  has  been  shown  that 
each  beat  of  the  heart  sends  impulses  up  to  the 
medulla  by  means  of  these  fibres  ;  in  addition  there 
are  some  special  fibres  from  the  root  of  the  aorta 
and  the  left  ventricle,  called  the  depressor  fibres  ; 
stimulation  of  these  causes  general  dilatation  of 
capillaries,  producing  marked  drop  in  blood-pressure, 
thereby  giving  instantaneous  relief  to  a  heart  beating 
against  a  pressure  too  high  for  its  powers. 


THE     IIKART  68 

Th(Te  is  no  doubt  that  pain  does  arise  in  the  heart 
itself,  but  the  precise  nature  of  the  pain-provoking 
stimuhis,  and  the  path  by  means  of  which  it  is  Hnked 
up  with  the  afferent  cardiac  nerves,  has  not  yet 
been  demonstrated. 

CARDIAC     IRREGULARITIES. 

Cardiac  irregularities  may  be  classified  according 
to  the  site  of  origin  of  abnormal  action  in  the  neuro- 
muscular elements  of  the  heart,  and  fall,  therefore, 
into  the  following  groups :  (i)  Irregiilarities  of 
ftervous  origin  ;  (2)  Defects  in  conductivity  ;  (3)  In- 
creased excitability  ;    (4)  Defects  in  contractility. 

I.  Irregularities  of  Nervous  Origin. — Experiments 
have  proved  that  stimulation  of  any  sensory  nerve 
affects  the  heart-rate.  In  life,  any  emotion,  move- 
ment of  the  body,  or  activity  of  organs  sends  impulses 
to  the  brain  by  the  sensory  nerves,  but  they  are  too 
small  to  bring  about  changes  of  the  heart-rate. 
Forced  movements,  and  great  emotions — such  as 
fright,  anger,  or  pain — produce  impulses  which  do 
affect  the  rate.  Stimuli  which  are  not  strong  enough 
to  cause  changes  in  rate  may  do  so  in  conditions  of 
nervous  instabiUty,  or  in  children.  Thus  ordinary 
breathing,  swallowing,  yawning,  digestive  activity, 
or  smoking  may  cause  irregularity  of  the  heart. 
This  irregularity  is  named  sinus  arrhythmia,  inasmuch 
as  it  is  caused  by  alteration  in  the  rate  of  stimulus 
production  in  the  sinu-auricular  node. 

This  type  of  arrhythmia  may  also  occur  in  menin- 
gitis, or  other  conditions  of  increased  intracranial 
tension,  in  tumours  pressing  on  the  vagus,  or  from 


THE    HEART 

drugs  such  as  digitalis.  Occasional!}'  cases  are  met 
with  in  which  stand-still  of  the  whole  heart  for  some 
seconds  has  been  caused  by  vagal  inhibition,  and  one 
case  has  been  recorded  where  cerebral  anaemia  from 
this  condition  caused  loss  of  consciousness  and  con- 
vulsiform  movements  such  as  occur  in  the  Stokes- 
Adams  syndrome.  Sinus  arrhythmia  is  easy  to 
-detect  in  polygraphic  tracings.  The  venous  pulse 
shows  that  each  beat  is  a  normal  sequence.  After  a 
series  of  rapid  beats  there  may  be  a  pause  suggesting 
the  pause  after  a  premature  beat  ;  but  on  accurate 
measurement  of  the  pulse  periods,  the  succeeding 
ones  will  be  seen  to  get  gradually  shorter  till  another 
series  of  rapid  beats  will  occur.  The  respiratory 
rhythm  can  usuall}^  be  seen  in  the  venous  tracing, 
and  the  periods  of  slow  and  quick  beats  may  be 
seen  to  correspond  with  inspiration  and  expiration. 
Respiratory  sinus  arrhythmia  is  extremely  common 
in  children. 

2.  Defects  in  Conductivity. — Defects  in  conductivity 
may  occur  either  from  nervous  influences — for  we  have 
seen  that  the  vagus  may  decrease  the  conductivity  of 
the  a-v  bundle — or  from  pathological  lesions  in,  or 
in  the  neighbourhood  of,  the  conduction  fibres.  The 
commonest  of  these  are  gumma,  aneurysm,  tumour^ 
acute  inflammatory  conditions,  fibrosis,  or  calcifica- 
tion. The  delay  may  be  of  an}^  intensity,  from  a 
mere  lengthening  of  the  a-c  or  P-R  interval  to 
complete  block. 

In  some  cases  of  rheumatic  heart  disease,  poly- 
graphic tracings  or  electrocardiograms  show  an 
increase  of  the  a-c  or  P-R  intervals  ;   if  the  process 


THE     HEART  65 

goes  a  stage  further,  a  ventricular  contraction  may 
be  observed  to  fail  occasionally  owing  to  conductivity 
not  having  recovered  in  time  to  carry  the  stimulus 
to  the  ventricular  muscle.  This  is  beautifully  shown 
in  tracings  ;  the  a-c  interval  is  gradually  increased 
with  each  successive  beat  until  a  ventricular  con- 
traction fails.  The  next  a-c  interval  is  normal,  or 
almost  so,  owing  to  the  long  pause  enabling  the 
bundle  to  recover  its  function  ;  but  then  the  steady 
increase  starts  again  till  another  contraction  is  missed, 
and  so  on.  If  a  heart  such  as  this  beats  more  slowlv, 
the  longer  diastole  gives  the  auriculoventricular 
bundle  more  time  to  recover,  and  the  heart-block 
decreases  ;  but  if  it  accelerates,  the  block  immediately 
becomes  more  intense. 

With  a  more  serious  defect  in  conductivity  the 
ventricle  may  drop  out  more  frequently,  and  may 
only  respond  once  to  two,  three,  or  more  beats  of 
the  auricle,  causing  a  2-1,  3-1,  4-1  heart-block. 

If  a  complete  block  occurs,  the  idioventricular 
rhythm  is  called  into  action,  while  the  auricles  con- 
tinue to  contract  at  the  dictation  of  the  sinu-auricular 
node.  There  is  often  a  pause  of  some  seconds  before 
the  idioventricular  rhythm  starts  ;  the  length  of  this 
seems  to  depend  on  (a)  The  suddenness  ^^•ith  which 
the  block  occurs  ;  and  [h)  The  healthiness  of  the 
ventricular  muscle.  The  more  suddenly  the  block 
occurs,  the  longer  the  ventricles  take  to  start  their 
own  rhythm,  and  healthy  muscle  appears  to  respond 
more  quickly  than  diseased  muscle.  The  loss  of  con- 
sciousness and  the  con\Tilsions  which  occur,  depend 
on  thejength  of  the  ventricular  pause,  for  they  are 


66  THE    HEART 

caused  by  the  cerebral  anaemia  resulting  from  the 
absence  of  the  pulse. 

The  idioventricular  rhythm  arises  somewhere 
between  the  auriculoventricular  node  and  the 
ventricular  muscle,  for  the  electrocardiogram  shows 
a  normal  ventricular  complex,  proving  the  beat  to 
have  arisen  somewhere  in  the  Purkinje  system  of 
fibres.  It  is  regular,  and,  as  a  rule,  about  30  per 
minute,  though  it  may  be  slower  or  quicker ;  one 
case  is  described  where  the  rate  was  60  per  minute. 
The  reason  for  this  variation  is  not  clear.  It  has 
been  proved  that  the  cardiac  nerves  have  no  effect 
on  the  idioventricalar  rhythm,  so  that  it  must  depend 
on  the  excitability  of  the  focus  giving  rise  to  the 
stimulus. 

The  regularity  of  this  rhythm  is  sometimes  inter- 
rupted by  premature  beats  occurring  at  a  certain 
time-interval  after  each  beat.  These  are  ventricular 
premature  beats  arising  in  the  ventricular  muscle, 
as  shown  by  the  electrocardiogram,  which  gives  an 
abnormal  complex  of  that  type.  The  pause  between 
the  premature  beat  and  the  next  idioventricular 
beat  is  always  of  the  same  length  as  that  of  a  cycle 
where  no  premature  beat  occurs. 

The  auricles  are  unaffected,  and  their  rate  of  beat 
is  stiU  governed  by  the  sinu-auricular  node,  the 
ventricular  beats  being  quite  independent  of  the 
auricles.  In  fact,  cases  have  been  described  where 
the  ventricles  have  been  beating  independently,  and 
the  auricles  have  been  fibrillating  or  fluttering. 

It  has  been  mentioned  that  during  the  inception 
of  the  idioventricular  rhythm  there  is  a  pause  in  the 


THK    HEART  67 

ventricles  of  some  seconds  ;  in  some  cases  this  recurs 
at  varying  periods  and  is  of  varying  length.  Patients 
often  die  during  one  of  these,  but  again  in  many 
cases  the  rhythm  goes  on  perfectly  regularly,  and  may 
remain  so  for  years,  till  the  patient  dies  of  some 
intercurrent  affection. 

This  \aries  with  the  lesion  causing  the  heart-block. 
If  the  lesion  is  a  progressive  one,  such  as  acute  inflam- 
mation, ulceration,  or  tumour,  it  may  spread  and 
cause  further  damage  to  the  Purkinje  system  at  a 
lower  level ;  but  an  unirritating  lesion,  such  as  fibrosis, 
scarring,  or  calcification,  will  remain  quiescent  after 
the  initial  damage. 

There  is  no  difficulty  in  recognizing  heart-block, 
partial  or  complete,  by  means  of  tracings  or  electrical 
curves.  In  partial  block  it  will  be  seen  that  no 
c  or  V  wave  occurs  during  the  radial  pause,  but  that 
the  a  wave  is  present  in  the  situation  expected. 
The  a-c  interval,  where  the  ventricle  contracts,  will 
also  be  seen  to  be  longer  than  normal.  In  complete 
block  the  a  waves  are  as  a  rule  well  marked,  and 
will  be  seen  to  occur  regularly  quite  independent  of 
the  ventricles,  which  beat  slowly  and  regularly 
unless  disturbed  by  premature  systoles.  These  can 
be  easily  recognized  in  the  radial  pulse. 

It  may  be  confounded  with  stand-still  of  the  whole 
heart  associated  with  vagal  inhibition  ;  but  the  absence 
of  a  waves  during  the  pause,  and  the  normal  sequence 
of  a,  c,  and  v  waves  when  a  contraction  does  occur, 
disclose  its  mechanism. 

Some  cases  of  complete  heart-block  have  been 
described  where  no  abnormality  has  been  found  in 


68  THE    HEART 

the  conduction  system  after  death  ;  and  again,  others 
have  been  recorded  where,  although  no  dissociation 
occurred  during  hfe,  severe  pathological  lesions  have 
been  demonstrated  in  the  auriculoventricular  node 
and  bundle  which  would  appear  to  have  completely 
destroyed  the  bundle.  These  cases  cannot  be 
accounted  for  by  our  present  knowledge. 

Pa.rtial  heart-block  is  in  many  cases  due  to  vagal 
depression  of  conductivity.  This  may  be  demon- 
strated by  injecting  -^V  S^.  atropine,  which  paralyzes 
the  nerve-endings  of  the  vagus.  If  due  to  this  cause, 
the  heart-block  passes  off  as  soon  as  the  rate  quickens 
and  conductivity  is  restored.  It  has  been  thought 
that  this  might  account  for  some  of  the  cases  of 
complete  heart-block  with  no  demonstrable  lesion  ; 
but  in  one  case  at  least  atropine  made  no  difference 
to  the  block,  and  yet  no  lesion  was  found  after  death. 

Partial  heart-block  has  been  recorded  in  a  number 
of  cases  of  rheumatic  carditis,  and  also  in  pneu- 
monia, influenza,  and  diphtheria.  It  usually  passes 
off  after  a  few  days. 

Complete  heart-block  occurs  in  acute  rheumatism, 
typhoid  fever,  pneumonia,  diphtheria,  ulcerative 
endocarditis,  and  in  gonococcal  septicaemia. 

Most  examples  of  heart-block,  of  all  degrees,  are, 
however,  met  with  in  chronic  disease  such  as  cardio- 
sclerosis and  cardiac  syphilis. 

3.  Irregularities  from  I'ncreased  Excitahility. — Any 
part  of  the  cardiac  musculature  which  is  in  a  state 
of  increased  excitability  may  give  rise  to  a  stimulus 
which  causes  contraction.  Thus  a  premature  con- 
traction may  arise  from  any  part,  and  may  therefore 


THE     HEART  66 

be  auricular,  ventricular,  or  nodal.  If  the  irritation 
be  severe,  it  may  lead  to  a  short  series  of  beats  from 
this  situation,  and  in  extreme  conditions  may  cause 
long  series  of  abnormal  beats,  or  in  other  words  the 
normal  rhythm  may  be  replaced  by  a  rhythm  start- 
ing from  the  irritable  focus,  and  paroxysmal  attacks 
of  tachycardia  originate. 

Single  Premature  Contractions. — Premature  con- 
tractions arise  from  the  initiation  of  a  stimulus  in 
any  part  of  the  musculature  of  the  heart ;  thus  they 
may  start  in  the  auricles,  ventricles,  or  the  auriculo- 
ventricular  bundle  or  node. 

The  site  of  origin  may  be  determined  from  poly- 
graphic  tracings.  In  auricular  extrasystoles  a 
premature  a  wave  is  found,  followed  by  a  c  wave, 
which  coincides  with  the  small  beat  in  the  radial. 
The  a-c  interv^al  is  usually  prolonged  owing  to  the 
conductivity  not  having  perfectly  recovered  its 
function  ;  the  earlier  in  diastole  the  premature  beat 
occurs,  the  more  prolonged  the  a-c  interval  will 
be. 

H  the  ventricles  beat  prematurely,  the  auricles 
contract  at  their  normal  time,  receiving  a  stimulus 
from  the  sinu-auricular  node,  and  the  ventricular 
beat  occurs  independently  of  the  auricular. 

When  polygraphic  tracings  are  studied,  it  will  be 
seen  that  the  ventricular  beat  may  occur  synchron- 
ously with  the  auricular,  or  the  a  wave  may  be  found 
slightly  after  the  c  wave.  In  these  cases  the  stimu- 
lus from  the  auricular  beat  falls  on  the  ventricle 
during  its  refractory  period,  and  the  ventricle  does 
not  contract  ;    hence  there  is  a  pause  till  the  next 


70  THE    HEART 

auricular  beat.  From  beat  to  beat,  excluding  the 
premature  contraction,  vdll  therefore  be  equal  to 
two  normal  beats.  This  is  what  is  known  as  a  fully- 
compensated  pause,  and  is  characteristic  of  ven- 
tricular premature  contractions. 

If  the  premature  beats  occur  early,  or  if  the  heart- 
rate  is  slow,  the  auricular  contraction  occurs  at  an 
appreciable  interval  after  the  ventricular  premature 
beat,  and  the  stimulus  may  fall  on  the  ventricle  after 
its  refractory  period,  in  which  case  the  ventricle  will 
contract,  and  a  normal  rhythm  is  seen,  save  that  one 
premature  ventricular  contraction  occurs  between 
two  normal  beats.  This  is  termed  an  interpolated 
premature  beat. 

If  the  venous  pulse  in  ventricular  premature  con- 
tractions be  studied,  we  find  either  one  large  wave 
corresponding  to  both  a  and  c  when  the  contractions 
recur  simultaneous!}",  or  the  a  wave,  though  in  its 
normal  situation,  as  ascertained  by  measurement, 
may  foUow  the  c  wave  of  the  premature  beat. 

We  have  seen  that  a  fuUy  compensatory  pause  is 
characteristic  of  ventricular  premature  beats ;  in 
premature  auricular  contractions  the  pause  is  not 
compensatory.  This  is  said  to  be  due  to  the  fact 
that,  if  a  stimulus  arises  in  the  muscular  wall  of  the 
auricle,  it  passes  back  to  the  sinu-auricular  node  and 
discharges  its  stimulus-producing  material  ;  conse- 
quently there  is  a  pause  till  the  next  stimulus  is 
produced  at  the  sinu-auricular  node  ;  the  complete 
pause  will  therefore  be  a  normal  pulse  period  plus 
the  time  taken  for  the  premature  stimulus  to  reach 
the    sinu-auricular    node.     If    the   premature   beat 


THE    HEART  71 

originates  in  the  sinu-auricular  node,    the  pause  i» 
found  to  be  exactly  a  normal  pulse  period. 

Beats  may  originate  in  the  conducting  mechanism 
of  the  heart,  either  as  escaped  beats  of  a  lower  pace- 
maker or  as  premature  contractions.  The  latter  are 
frequently  found  arising  from  the  auriculo-ventricular 
node.  The  stimulus  is  conducted  both  ways — back 
to  the  auricles  and  forward  to  the  ventricles — and 
these  chambers  contract  almost  or  quite  simul- 
taneously. 

In  polygraphic  tracings  we  find  one  large  wave 
due  to  a  and  c,  as  in  some  ventricular  premature 
beats,  but  in  this  case  both  a  and  c  will  be  premature. 
The  auricle  may  beat  shortly  before  the  ventricle, 
but  the  a-c  interval  is  o'l  or  under.  There  will  be 
no  sign  of  an  a  wave  in  its  normal  place  as  there  is 
in  the  ventricular  premature  beats. 

Electrocardiograms  of  premature  contractions  are 
even  more  satisfactory  than  polygraphic  tracings  for 
diagnosing  the  site  of  origin.  An  auricular  premature 
beat  will  give  an  abnormal  auricular  complex  and 
a  normal  ventricular  complex,  while  all  ventricular 
premature  beats  give  abnormal  complexes,  and  the 
type  of  complex  will  locate  the  position  of  the  focus 
initiating  the  beat.  A-v  or  nodal  premature  beats 
usually  show  an  inverted  auricular  complex  occurring 
just  before  the  R  of  the  ventricular  complex. 

The  cause  of  premature  beats  is  not  perfectly 
determined.  We  know  from  experiment  that  elec- 
trical stimulation  and  other  methods  which  cause 
an  irritable  focus  will  produce  them,  but  they  occur 
in  healthy  as  well  as  in  unhealthy  hearts.     There  is 


72  THE    HEART 

vsome  reason  to  think  that  over-distention  of  a 
cardiac  chamber  may  provoke  it  to  premature 
contraction. 

For  instance,  auricular  premature  beats  are  verv 
common  in  mitral  stenosis,  where  the  auricle  has 
difficulty  in  emptying  itself  and  is  therefore  fuller 
than  in  health  ;  but  one  cannot  exclude  the  possi- 
bility of  disease  of  the  auricular  wall. 

Again,  in  any  case  with  frequently  recurring 
premature  beats  of  one  type,  the  time  relation  of  the 
abnormal  beat  to  the  preceding  beat  is  usually  the 
same.  This  points  to  some  causal  connection  be- 
tween the  previous  beat  and  the  premature  beat. 

Nodal  extrasystoles  cannot  be  due  to  over  dis- 
tension ;  they  are  not  met  with  nearly  so  frequently, 
and  are  probably  due  to  some  functional  or  organic 
irritative  lesion  in  the  auriculo ventricular  node  or 
in  the  blood-vessels  suppl3dng  it. 

Premature  beats  are  common  in  adults  and  older 
people,  but  not  in  young  children.  Acceleration 
due  to  exercise  tends  to  diminish  them  in  healthy 
hearts,  but  to  increase  them  in  hearts  showing  signs 
of  overwork.  The  general  opinion  is  that  in  health 
they  have  no  significance,  but  that  in  hearts  whose 
reserve  of  power  is  failing  they  indicate  disease 
in  the  muscle,  and  that  they  may  lead  on  to  more 
and  more  frequent  premature  beats,  occurring  at 
first  every  few  beats  ;  then  short  runs  of  premature 
beats  appear,  and  later  long  paroxysms  of  abnormal 
rhythms  set  in. 

A  few  cases  have  been  followed  through  where 
electrocardiograms  of  a  premature  beat  of  a  certain 


THE     HEART  73 

type  have  been  demonstrated,  and  later  on  paroxysms 
of  tachycardia  have  been  shown  to  consist  of  a  series 
of  beats  identical  in  form  with  the  original  premature 
beats.  Thus  there  can  be  little  doubt  that  premature 
beats  may  lead  on  to  prolonged  abnormal  rhythms. 
The  paroxyms  may  originate  from  the  auricle, 
ventricle,  or  auriculoventricular  node. 

Auricular  tachycardia  or  auricular  flutter,  as  the 
more  rapid  tachycardias  are  now  called,  is  by  no 
means  uncommon.  Rates  varying  from  i6o  to  460  or 
more  have  been  described,  and  proved  by  means  of 
electrocardiographic  curves.  The  ventricle  does  not 
respond  to  every  auricular  beat,  as  heart-block  of 
2,  3,  4,  or  5  to  I  grade  may  be  present,  thus  acting  as 
a  protective  mechanism  ;  for  the  heart  would  rapidly 
f^  if  the  ventricle  tried  to  contract  to  each  auricular 
contraction.  This  fact  causes  difficulty  in  diagnosis, 
as  shown  in  the  following  case  seen  by  us  not 
long  ago.  A  woman  suffering  from  mitral  stenosis 
with  a  considerable  amount  of  heart  failure  gave  a 
history  of  periodic  attacks  of  palpitation  and  a  feeling 
of  very  rapid  heart  action.  Her  heart  was  beating 
at  72  per  minute,  and  was  perfectly  regular.  It  was 
thought  that  these  attacks  were  due  to  paroxysmal 
tachycardia,  but  an  electrocardiogram  showed  that 
the  auricular  rate  was  216.  The  attacks  were  due 
to  the  grade  of  heart-block  decreasing  and  the 
ventricle  taking  up  the  auricular  rhythm. 

This  case  demonstrates  that  for  accurate  diagnosis 
it  is  essential  to  use  graphic  methods.  Occasionally 
rapid  movements  of  the  veins  in  the  neck  may  give  a 
clue  to  this  condition,  and  the  waves  are  often  shown 


74  THE    HEART 

in  venous  curves,  but  in  the  majority  of  cases 
certainty  of  diagnosis  can  only  be  attained  by  the 
electrocardiogram.  Probably  all  cases  with  attacks 
of  tachycardia  where  the  quick  rate  is  a  multiple  of 
the  slow  rate  are  due  to  this  condition. 

The  heart  is  not  always  regular,  as  the  grade  of 
heart-block  may  vary  from  time  to  time  or  from 
beat  to  beat.  This  may  disclose  the  nature  of  the 
irregularity,  as  the  varying  pulse  periods  bear  an 
arithmetical  relationship,  being  all  multiples  of  one 
auricular  contraction  period. 

The  attacks  may  begin  and  end  suddenly, 
giving  a  paroxysm  of  auricular  tachycardia,  or  they 
may  continue  for  long  periods.  When  they  cease, 
they  may  be  replaced  by  a  normal  sinus  rhythm  or 
by  auricular  fibrillation.  Full  doses  of  digitalis  seem 
to  cause  the  onset  of  fibrillation,  and  if  the  drug  be 
then  withheld,  the  heart  often  jumps  back  to  a 
normal  rhythm. 

Paroxysms  of  ventricular  tachycardia  are  rare,  but 
are  of  interest  physiologically,  inasmuch  as  a  retro- 
grade beat  of  the  heart  is  set  up  after  the  first  four 
or  five  beats,  and  the  auricle  then  responds  to  a 
stimulus  conducted  backwards  from  the  ventricles, 
the  sinus  rhythm  being  for  the  time  in  abeyance. 
At  the  end  of  the  paroxysm  there  is  a  pause,  and 
then  the  sinu-auricular  node  takes  on  control.  The 
condition  can  only  be  diagnosed  with  certainty  by 
the  electrocardiograph,  which  shows  an  abnormal 
type  of  ventricular  complex. 

Paroxysms  of  7wdal  tachycardia  also  occur,  each 
beat  of  which  is  the  replica  of  a  nodal  premature 


THK     ffEAKT  75 

beat.  The  paroxysms  start  and  end  suddenly,  and 
there  is  a  pause  between  the  offset  of  the  abnormal 
rhythm  and  the  onset  of  sinus  rhythm. 

In  studying  the  effect  these  rhythms  have  on  the 
heart  and  circulation,  one  must  take  into  account 
the  state  of  the  heart  prior  to  the  attack.  If  the 
reserve  force  of  the  heart  is  fair,  a  paroxysm  rarely 
gives  rise  to  any  signs  of  heart  failure  till  it  has 
lasted  some  considerable  time  ;  but  this  also  depends 
to  a  great  extent  on  the  rate  of  the  tachycardia.  A 
rate  of  over  200  will  cause  signs  very  much  more 
quickly  than  one  under  ;  but  most  patients,  provided 
they  lie  down  during  the  attack,  show  very  few  signs 
of  distress  and  very  rapidly  regain  their  accustomed 
activity  after  the  attack  is  over.  If  the  heart  be 
failing  before  the  onset,  an  attack  very  soon  puts 
them  in  a  critical  condition.  The  tone  and  con- 
tractile power  become  exhausted,  the  ventricles  are 
not  properly  filled,  the  circulation  accordingly  slows, 
there  is  stasis  of  blood  in  the  capillaries  and  veins, 
tenderness  and  enlargement  of  the  liver  occur, 
cyanosis  and  oedema  appear,  and  death  may  ensue 
unless  the  paroxysm  ceases. 

Auricular  flutter  does  not  have  much  effect  on  the 
heart  or  the  circulation  provided  the  heart-block 
keeps  the  xentricle  slow  ;  but  should  this  become 
rapid,  the  same  effects  as  in  the  other  tachycardias 
appear. 

Auricular  fibrillation  is  a  condition  in  which  the 
auricles  cease  to  contract  co-ordinately.  They  dilate, 
and  individual  fibres  or  groups  of  fibres  appear 
to    contract    in    an    irregular   manner,   so   that  the 


76  THE    HEART 

auricular  muscle  appears  to  be  in  a  state  of  continual 
tremor,  like  a  muscle  undergoing  progressive  muscu- 
lar atrophy. 

The  ventricles  contract  in  a  continuously  irregular 
manner,  both  as  to  rhj^thm  and  force  ;  thus  no  two 
beats  of  the  same  length  appear  consecutively,  nor 
is  there  any  true  relationship  between  beats  or  groups 
of  beats  as  in  auricular  flutter.  A  longer  pause  is 
often  followed  by  a  small  beat,  while  a  short  pause 
may  be  succeeded  by  a  larger  beat. 

This  ventricular  irregularity  is  caused  by  the  irregu- 
lar stimuli  arriving  from  the  fibrillating  auricles.  It 
very  commonly  occurs  in  the  later  stages  of  rheu- 
matic heart  disease — more  particularly  mitral  stenosis 
— ^but  has  been  known  to  occur  during  the  first 
attack  of  acute  rheumatism  in  a  child.  It  appears 
frequently  in  hypertrophied  hearts  where  the  muscle 
is  degenerated.  Attacks  may  be  paroxysmal  at 
first,  but  more  often  the  condition  ha\dng  once 
started  remains  permanently.  It  has  been  known 
to  last  for  fifteen  or  more  years. 

In  cases  where  some  degree  of  defective  con- 
ductivity is  present,  a  var^^ing  number  of  the 
irregular  stimuli  may  be  blocked  by  the  conducting 
bundle,  and  the  ventricular  rhythm  may  be  slow, 
though  being  still  absolutely  irregular.  If  the  block 
is  complete,  the  idioventricular  rhythm  will  be 
present  and  the  ventricles  regular.  The  actual 
cause  of  the  condition  is  not  definitely  known, 
though  several  hypotheses  have  been  put  forward^ 
The  chief  of  these  are  : — 

(a)  That  the  auricular  muscle  is  in  an  extremely 


THK     HEART  77 

excitable  and  irritable  state,  and  that  stimuli  are 
produced  at  many  sites  in  the  auricle  at  the  same 
time,  thus  causing  inco-ordination.  (b)  That  the 
conduction  from  fibre  to  fibre  in  the  muscle  may  be 
blocked  in  varying  degree  ;  thus,  the  wave  of  con- 
traction would  travel  at  varying  rates  in  different 
parts  of  the  muscle.  This  would  cause  inco-ordina- 
tion. (c)  That  disease  of  the  sinu-auricular  node 
may  cause  irregularity  in  the  excitation  of  the 
muscle.  The  first  seems  to  be  the  most  likely,  as 
it  agrees  best  with  the  clinical  and  histological  facts. 

The  condition  is  easily  diagnosed.  The  absolutely 
irregular  pulse  is  characteristic.  A  tracing  shows 
the  ventricular  type  of  venous  pulse  with  absence 
of  the  a  wave.  During  the  longer  diastoles,  small 
irregular  waves  may  be  sometimes  seen.  These  are 
caused  by  the  inco-ordinate  contractions  of  the 
auricles. 

An  electrocardiogram  shows  normal  ventricular 
complexes  as  the  stimulus  is  conveyed  to  the 
ventricle  by  the  bundle.  There  is  no  P  wave,  but 
small  irregular  deflections  are  seen  all  through 
diastole,  corresponding  to  the  small  waves  sometimes 
present  in  the  venous  pulse. 

Ventricular  fibrillation  occurs  in  cases  of  chloroform 
poisoning,  and  also  in  experimental  occlusion  of  the 
coronary  arteries.  It  is  possibly  the  cause  of  death 
in  many  cases  of  heart  failure. 

4.  Defects  of  Contractility. — Pulsus  alternans  is 
stated  to  be  due  to  a  defect  in  ventricular  con- 
tractihty.  It  consists  of  an  alternation  of  small  and 
larger  beats,  the  rhythm  being  regular.    It  is  found  : 


78  THE    HEART 

[a)  In  hearts  failing  against  a  high  blood-pressure  ; 
{b)  In  rapid  rhythms  such  as  paroxysmal  tachy- 
cardias ;    (c)  In  some  cases  after  premature  beats. 

A  continuous  pulsus  alternans  is  a  sign  of  weaken- 
ing of  the  ventricular  muscle,  and  is  a  danger  signal. 
Recently  a  group  of  cases  showing  this  rhythm  was 
described  (Windle).  Of  13  cases  in  which  the  onset 
of  pulsus  alternans  was  noticed,  9  were  fatal,  in 
periods  of  from  one  month  to  two  years.  Four  were 
still  under  observation,  and  the  longest  period  that  it 
had  existed  was  twenty- three  months.  Of  18  other 
cases  where  this  symptom  was  noted  on  the  first 
examination,  12  died  within  nine  months,  i  in 
twenty-one  months ;  the  remaining  5  were  still 
alive,  but  the  longest  period  of  observation  was 
eighteen  months. 

Of  the  fatal  cases,  some  did  not  seem  very  ill  at 
the  time  of  onset  of  this  sign,  which  is  therefore 
always  of  grave  omen. 

We  may  now  sum  up  the  prognostic  significance 
of  the  various  cardiac  arrhythmias  with  the  follow- 
ing proviso.  An  arrhythmia  per  se  does  not 
necessarily  alter  the  prognosis  at  all,  but  must  be 
considered  in  conjunction  with  aU  the  other  features 
of  the  case. 

Sinus  arrhythmia  may  be  considered  as  a  normal 
phenomenon  in  children  and  young  adults. 

Heart-block  is  nearly  always  a  sign  of  grave  disease, 
but  the  immediate  prognosis  of  a  complete  and 
stationary  block  is  relatively  good. 

Premature  contractions  in  otherwise  normal  hearts 


THE     HEART  79 

mean  nothing  ;  but  where  heart  disease  exists,  and 
the  loss  of  reserve  cardiac  power  is  serious,  the 
development  of  premature  contractions  increases  the 
gravity  of  the  prognosis. 

Auricula)'  flutter  is  an  abnormal  action  of  the 
heart  occasioned  by  serious  disease ;  but  provided 
that  an  accompanying  block  keeps  the  ventricular 
rate  slow,  the  immediate  prognosis  of  the  case  is  not 
altered. 

Auricular  fibrillation,  unless  accompanied  by 
heart-block,  rapidly  leads  to  cardiac  failure  from 
ventricular  exhaustion.  The  prognosis  depends  upon 
the  reaction  to  drugs.  If  the  digitalis  group  slow^s 
the  heart,  prognosis  is  fair,  provided  the  drug  can  be 
continuously  taken.  If  digitalis  and  its  allies  do 
not  cause  slowing,  the  prognosis  is  bad. 

Pulsus  alternans  is  of  grave  prognostic  significance. 


80 


CHAPTER    IV. 
SURGICAL     SHOCK. 

WHAT  IS  SHOCK  ?— ^THE  PHENOMENA  OF  SHOCK — EXPERI- 
MENTAL MEANS  OF  INDUCING  SHOCK-LIKE  CONDITIONS 
—THEORIES  AS  TO  ITS  NATURE — PREVENTION  AND 
TREATMENT— INTRAVENOUS    SALINE    TRANSFUSION. 

NO  scientific  problem  more  interesting  to  phy- 
siologists and  clinicians  alike  came  before  the 
notice  of  the  profession  during  the  war  than  that 
presented  by  surgical  shock.  It  was  so  frequent,  so 
deadly,  and  withal  so  elusive,  that  an  immense 
amount  of  study  was  devoted  to  the  subject  from 
many  different  points  of  \'iew,  and  this  chapter  is 
completely  rewritten  in  consequence.  Real  progress 
has  been  made  ;  some  more  or  less  settled  conclusions 
have  been  arrived  at ;  ancient  theories  have  dis- 
appeared. Yet  it  cannot  be  said  that  we  are  much 
nearer  the  solution  of  some  of  the  most  important 
problems  of  all.  This  is  rather  surprising,  seeing 
that  we  had  the  best  young  brains  of  Europe  and 
America  enlisted  in  the  research,  and  such  material 
as  the  world  has  never  furnished  before,  and  pray 
Heaven  may  never  furnish  again.  Who  of  us  that 
saw  it  ^vill  ever  forget  the  dimly-lighted,  silent  tents 
or  huts  that  formed  the  '  shock-ward  '  at  a  casualty 
clearing  station  on  the  night  after  some  great  battle  ? 
One  reason  for  the  difficulty  has  been  a  difference 
of  understanding  as  to  what  we  mean  by  '  shock'. 


SURGICAL    SHOCK  81 

The  patients  who  came  down  from  the  field 
ambulances  were  very  *  bad ',  often  dying,  or  they 
became  so  within  a  day  or  two  ;  but  cases  of  pure 
shock  were  rather  rare,  and  much  of  the  '  bad  '-ness 
was  not  due  to  shock  at  all.  The  following  con- 
ditions have  to  be  excluded  or  allowed  for  before  we 
can  agree  that  shock  is  present  : — 

1.  Considerable  loss  of  blood.  Loss  up  to  a  pint 
does  not  by  itself  do  any  harm  to  a  healthy  young 
man,  as  we  know  from  its  slight  effects  on  donors  for 
blood-transfusion.  A  small  loss  will,  however, 
jeopardize  the  life  of  a  man  with  grave  bodily 
injuries. 

2.  Concussion  of  brain,  spinal  cord,  or  thorax. 

3.  Toxc^mia  from  intestinal  paralysis  and  con- 
sequent absorption.  Grave  symptoms  coming  on  a 
day  or  two  after  a  sev^ere  abdominal  injury  or  opera- 
tion are  usually  due  to  this  cause,  not  shock. 

4.  Syncope  from  mental  effects,  such  as  fainting 
from  a  slight  or  severe  wound.  This  is  a  transient 
condition,  and  the  patient  recovers  in  a  few  hours, 
often  in  a  few  minutes. 

5.  ToxcBmia  from  acute  infections.    During  the  war, 
streptococcal  or  gas-gangrene  infections  of  wounds, 
especially  wounds  of  the  muscles  of  the  buttock  o 
leg,  gave   rise   to   shock-like   symptoms  coming   on 
usually  on  the  second,  third,  or  fourth  day. 

When  all  the  above  have  been  deducted,  there  is 
still  something  left,  but  at  a  casualty  clearing  station 
one  or  other  of  these  factors  would  account  for  more 
than  half  the  phenomena  of  so-called  '  shock '.  In 
civil    practice,     where    haemorrhage    and    virulent 

6 


82  SURGICAL    SHOCK 

infections  are  less  in  evidence,  shock  is  relatively 
infrequent  ;  but  when  it  occurs  it  usually  does  so  in 
a  purer  form.  The  best  examples  of  uncomplicated 
shock  are  seen  within  the  first  twenty-four  hours  of 
an  abdominal  injury,  after  such  an  operation  as 
amputation  at  the  hip-joint  or  Wertheim's  pan- 
hysterectomy for  cancer,  and  in  big  smashes  without 
an  open  wound.  In  bums,  the  picture  is  compli- 
cated by  blood-scorching. 

Surgical  shock,  then,  is  a  condition  of  depressed 
vitality  due  to  injury,  but  apart  from  the  above- 
mentioned  more  tangible  causes. 

THE     PHENOMENA     OF     SHOCK. 

The  well-known  signs,  such  as  pallor,  loss  of 
muscular  power  and  tone,  some  blunting  of  the 
mind,  quick  weak  pulse,  subnormal  temperature, 
reduced  urine,  etc.,  need  merely  be  mentioned  in 
passing.  They  are  familiar.  The  knee-jerks  are 
generally  normal,  but  in  profound  shock  they  may 
disappear. 

The  most  convenient  sign  of  shock  for  demonstra- 
tion purposes  and  for  the  sake  of  comparison  with 
other  cases  is  the  fall  of  blood-pressure  measured  by 
the  sphygmomanometer.  If  the  systolic  pressure  falls 
below  90,  the  condition  is  serious.  It  is  probable, 
however,  that  shock  may  be  present  before  the 
blood-pressure  falls,  though  it  is  difficult  to  recognize 
its  presence,  except  that  the  patient  may  ' look  bad'. 
This  is  important,  because  we  all  know  that  a  man 
may  be  sent  off  the  operating-table  with  a  good  pulse, 
but  already  his  life  is  in  danger,  and   a  few  hours 


SURGICAL    SHOCK  83 

later  he  collapses  and  dies  more  or  less  suddenly, 
On  the  other  hand,  a  fall  of  blood-pressure  does  not 
necessarily  prove  shock.  Turning  a  patient  on  his 
stomach  to  excise  a  wound  in  the  back  after  perform- 
ing a  laparotomy  for  gunshot  injury  used  to  cause  a 
serious  fall  of  blood-pressure,  but  this  was  quite 
probably  due  to  syncope,  and  rapid  recovery  some- 
times took  place,  though  of  course  syncope  is 
occasionally  fatal. 

Great  attention  has  been  paid  to  the  condition  of 
the  heart  and  blood-vessels  in  shock.  It  is  universaUy 
admitted  that  the  heart  is  not  primarily  at  fault. 
It  responds  gallantly  to  every  call  upon  it,  and 
becomes  quite  active  after  a  big  transfusion. 

The  ancient  controversy  as  to  whether  the  arteries 
are  dilated  or  contracted  in  shock  may  be  taken  as 
settled— they  are  contracted.  Indeed,  there  was 
never  any  evidence  to  the  contrary — only  theories. 
The  superficial  veins  are  contracted,  and  often  in 
a  state  of  active  spasm,  especially  in  the  hsemorrhage- 
shock  combination.  It  may  be  quite  difficult  to  find 
the  vein  for  transfusion  purposes,  and  having  found 
it  one  may  be  able  by  considerable  force  to  drive 
fluid  an  inch  or  two  along  it,  but  the  spasm  prevents 
it  from  going  any  further.  This  may  obtain  when 
it  is  quite  certain  that  the  cannula  is  in  the  lumen, 
not  in  the  vein  wall.  I  have  more  than  once,  for  this 
reason,  had  to  resort  to  the  saphena  vein  at  the  groin, 
to  give  a  blood-transfusion,  and  even  that  may  be 
found  extremely  contracted.  I  have  seen  the  con- 
dition in  pure  shock  apart  from  haemorrhage. 

It  has  been  theorized  for  years  that  the  abdominal 


84  SURGICAL    SHOCK 

vessels  are  dilated  in  shock,  and  that  most  of  the 
blood  in  the  body  collects  there.  Surgeons  nearly 
all  agree  that  this  is  not  true.  In  laparotomies  for 
acute  abdominal  catastrophes  and  for  early  gunshot 
injuries,  one  seldom  if  ever  notices  conspicuous  con- 
gestion of  the  blood-vessels  apart  from  peritonitis. 
Nor  is  the  liver  found  engorged  either  at  operation 
or  post  mortem. 

The  condition  of  the  capillaries  opens  up  some  new 
and  very  interesting  problems.  The  main  difficulty 
in  accounting  for  the  phenomena  of  shock  is  how 
to  reconcile  the  falling  blood-pressure  with  the 
mechanical  facts  of  the  case — the  heart  is  beating 
strongly ;  the  arteries  and  veins  are  contracted  ; 
the  blood  has  not  collected  unduly,  either  in  the 
abdomen  or  elsewhere.  As  we  shall  see,  Dale  has 
discovered  that  a  shock-like  condition  may  be  pro- 
duced in  animals  by  a  drug  called  histamine,  and 
here  also  the  heart  is  sound,  the  arteries  are  con- 
tracted, but  the  blood-pressure  faUs.  In  histamine 
poisoning  the  capillaries  appear  to  be  dilated  though 
the  arteries  are  contracted.  Some  other  chemical 
substances  act  similarly.  Apart  from  drugs,  there 
is  evidence  that  the  calibre  of  the  arteries  and  the 
capillaries  may  vary  independently  one  of  the  other. 
A  few  hours  or  days  after  section  of  the  sciatic  nerve 
in  a  cat,  the  pads  of  the  foot  on  the  operated  side 
are  paler  (=  capillary  contraction),  though  that  paw 
is  warmer  than  the  other,  not  only  to  the  touch,  but 
also  to  exact  measurement,  for  if  both  paws  are 
immersed  in  water  in  test-tubes,  the  water  on  the  side 
of  the  denervated  paw  is  warmed  up  more  quickly 


SURGICAL    SHOCK  85 

than  the  other  (=  arterial  dilatation  with  capillary 
contraction  on  the  operated  side).  This  opens  up 
the  possibility  that  the  capillaries  may  be  dilated  in 
shock,  which  if  true  might  account  for  the  fall  in 
blood-pressure. 

Cannon  and  others  have  made  red-cell-counts  of 
the  blood  of  patients  with  the  shock-haemorrhage 
complex,  and  find  that  there  may  be  a  higher  count 
of  corpuscles  in  the  capillaries  than  in  the  veins. 
The  same  has  been  reported  in  the  capillaries  of  the 
intestinal  villi  of  shocked  animals.  That  this  dis- 
parity may  occur  is  undoubted  ;  it  suggests  either 
that  the  force  of  the  circulation  is  not  enough  to 
move  on  the  corpuscles  from  the  narrow  capillaries, 
or  else  that  the  plasma  exudes  out  through  their 
walls,  leaving  the  corpuscles  behind.  That  this  is 
the  main  cause  of  the  fall  in  blood-pressure  seems 
very  improbable.  In  four  out  of  five  shock  cases  at 
a  casualty  clearing  station  in  France,  my  colleagues 
and  I  failed  to  find  any  difference  in  the  vein  and 
capillary  count.  If  the  capillaries  were  markedly 
dilated,  one  would  expect  the  mucous  membranes 
to  be  flushed  and  to  bleed  easily,  but  as  a  matter 
of  fact  they  are  pale  and  scarcely  bleed  at  all. 

It  is  widely  believed  that  the  total  blood-volume 
in  shock  is  reduced,  and  that  here  lies  the  explanation 
of  the  fall  in  blood-pressure.  It  may  be  that  this 
view  is  correct,  but  it  appears  to  have  been  too 
readily  accepted.  The  older  experimental  work  on 
the  subject  was  far  from  satisfactory,  though  it  is 
repeatedly  quoted.  My  own  observations  on  the 
specific  gravity  of  the  blood  during  the  onset  of  pure 


86  SURGICAL    SHOCK 

shock,  even  in  fatal  cases,  show  no  concentration, 
except  in  extensive  burns,  where  there  may  be  loss 
of  fluid  from  the  damaged  surface,  and  scorching  of 
the  plasma.  Only  once  did  I  meet  with  an  abnor- 
mally high  blood-count  in  a  shock  case  in  France. 
According  to  Guthrie,  in  experiments  on  shocked 
animals  there  is  an  increase  of  the  blood-volume,  up 
to  20  per  cent.  Observations  by  the  \dtal-red  method 
are  urgentl}^  required  ;  several  American  workers 
(Keith,  Robertson,  and  others)  have  shown  that 
there  is  a  fall  in  the  total  blood-volume  in  cases  of 
the  shock-haemorrhage  complex,  which  of  course  is 
only  to  be  expected,  but  I  have  not  yet  seen  any 
satisfactory  reports  of  estimations  in  pure  shock 
cases  in  the  human  subject. 

Keith  showed  that  if  the  blood-volume  is  75  per 
cent  of  the  normal  or  o\'er,  the  blood-pressure  is 
usually  above  95  mm.  of  Hg,  and  recovery  is  probable  ; 
a  blood-volume  between  65  and  75  per  cent  of  the 
normal,  with  a  blood-pressure  below  90,  means  that 
the  condition  is  grave,  and  if  the  blood-volume  falls 
below  65  per  cent,  blood-pressure  below  60,  recovery 
is  very  improbable.  I  found  the  total  blood- volume 
in  a  fatal  case  of  shock-haemorrhage  as  low  as  three 
pints.  Erlanger  and  Gasser,  in  cases  of  pure  shock  in 
experimental  animals,  find  that  the  blood-volume  is 
reduced  to  So  per  cent,  but  there  is  no  rise  in  per- 
centage of  blood-proteins  or  blood-corpuscles. 

It  is  quite  clear,  therefore,  that  the  vital-red 
method  does  not  give  the  whole  blood-volume,  but 
only  the  volume  of  the  actively  circulating  blood ; 
a  good  deal  is  evidently  l}dng  in  a  stagnant  back- 


SURGICAL    SHOCK  87 

water  in  some  capillary  areas,  probably  the  muscles, 
intestinal  villi,  and  other  viscera.  There  is  little,  if 
any,  loss  of  water  to  the  circulating  blood,  so  the 
blood-count  and  specific  gravity  do  not  rise.  The 
vital-red  evidently  does  not  reach  the  stagnant  area. 

This  capillary  stagnation  may  or  may  not  give 
rise  to  a  high  blood-count  in  the  skin-capillaries  ;  in 
my  experience  of  war  and  civilian  cases  it  usually 
does  not. 

As  Keith  has  shown,  the  virtual  loss  of  circulating 
blood-volume  due  to  stagnation  cannot  be  due  to 
haemorrhage  alone.  A  blood-donor  may  give  as 
much  as  800  c.c,  and  yet  his  blood- volume  may  be 
made  up  to  normal  within  an  hour. 

The  stagnation  in  the  visceral  and  muscle  capil- 
laries has  not  yet  been  conclusively  demonstrated 
by  histology  in  man,  though  Turck  gives  some 
pictures  of  it.  Certainly  it  does  not  occur  in  the 
brain  capillaries. 

Metabolism  in  Shock. — Evidence  has  accumulated 
that  important  chemical  changes  take  place  when 
the  blood-pressure  falls.  Both  in  experimental 
animals  and  in  wounded  soldiers  there  is  quite  con- 
stantly a  considerable  degree  of  acidosis.  This  has 
been  demonstrated  by  Cannon  and  others,  using  the 
van  Slyke  apparatus  and  technique,  which  shows 
a  fall  in  the  alkali  reserve  of  the  blood.  These  obser- 
vations were  verified  by  O.  H.  Robertson  at  the 
casualty  clearing  station  where  I  was  posted.  Dukes 
and  I  also  made  analyses  of  the  ammonia  nitrogen 
in  the  urine,  which  is  a  well-recognized  indicator  of 
acidosis,  and  found  a  very  marked  rise,  which  only 


88  SCJRGICAL    SHOCK 

comes  on  after  the  blood-pressure  falls,  and  increases 
as  the  shock  deepens.  We  found  that  the  acid  is 
neither  lactic  nor  diacetic.  There  is  some  evidence 
that  amino-acids  are  being  excreted  in  excess  (Lovell). 

It  does  not  appear  that  the  acidosis  is  the  primary 
cause  of  the  symptoms  in  shock.  In  point  of  time 
it  follows  rather  than  precedes  the  circulatory 
depression.  Higher  degrees  of  acidosis  may  be 
obtained  experimentally  \vithout  causing  the  animal 
any  inconvenience.  Alkaline  transfusion  is  little  if 
any  more  successful  than  saline  transfusion  in  the 
treatment  of  shock. 

B.  Moore  maintains,  not  ver^^  convincingly,  that 
there  is  really  an  alkalosis,  not  an  acidosis. 

Changes  in  Nerve-cells. — Crile  and  Dolley  have 
described  loss  of  the  Nissl  granules  and  other  signs 
of  exhaustion  in  the  cells  of  Purkinje  in  the  cere- 
bellum in  human  and  animal  cases  of  shock,  and 
similar  changes  have  been  observed  by  Mott  in  other 
nerve  centres.  I  have  worked  over  the  central 
nerv^ous  system  in  detail  in  four  cases  of  shock, 
and  some  controls.  The  first  was  a  patient  with 
multiple  simple  fractures  after  a  heavy  fall,  the 
second  a  crushed  chest,  the  third  a  gunshot  injury 
of  the  spine  and  abdomen  with  haemorrhage  as 
weU  as  shock.  They  all  died  within  twenty-four 
hours.  In  each  case  the  findings  were  concordant  ; 
the  nerve-cells  of  the  spinal  cord,  the  posterior  root 
ganglia,  and  the  motor  areas  and  nuclei  of  the  brain 
showed  no  abnormality,  but  the  sensory  cells  of  the 
brain  showed  a  profound  loss  of  Nissl  granules 
(gracile  and  cuneate  nuclei,   optic  thalamus).     The 


SURGICAL    SHOCK  89 

suggested  explanation  is  that  they  were  exhausted 
by  a  bombardment  of  painful  sensory  messages. 
Other  cells  showed  less  marked  changes — the 
Purkinje  cells  of  the  cerebellum,  Deiters'  nucleus, 
etc.     In  one  case  the  vagus  nucleus  had  suffered. 

In  a  fourth  case,  a  labourer  with  a  smashed  sacrum, 
compound  fracture  of  the  femur,  and  considerable 
retroperitoneal  and  external  haemorrhage,  death  was 
delayed  till  the  second  day,  and  the  Betz  cells  were 
more  severely  affected,  but  the  motor  nerve  nuclei 
escaped. 

EXPERIMENTAL     MEANS     OF     INDUCING 
SHOCK-LIKE     CONDITIONS. 

It  is  not  easy  to  induce  typical  shock  in  experi- 
mental animals  by  procedures  analogous  to  those 
which  give  rise  to  it  in  man.  According  to  Guthrie, 
even  crushing  the  brachial  or  sciatic  plexuses  often 
fails  to  lead  to  a  fall  of  blood-pressure,  and  multiple 
amputations  of  limbs  high  up  are  also  unreliable. 
The  most  constant  experimental  method  of  causing 
a  marked  fall  of  blood-pressure  that  will  go  on  to  a 
fatal  termination  if  the  stimulus  is  persisted  in,  is 
pulling  and  twisting  of  the  intestines,  but  it  needs 
to  be  prolonged. 

Several  workers  show  that  ligature  of  a  limb 
followed  by  crushing  of  the  muscles,  and  then  release 
of  the  ligature,  with  massage,  so  as  to  flood  the 
circulation  with  crush-products,  is  productive  of  a 
shock-like  condition  (Turck,  Bayliss,  Cannon).  There 
is  a  fall  of  blood-pressure,  lowered  temperature,  and 
sometimes  even  death.     If  the  ligature  is  kept  on. 


90  SURGICAL    SHOCK 

and  the  limb  amputated,  no  such  symptoms  are 
observed.  Grafting  in,  or  injecting  extracts  of,  the 
crushed  muscle  produces  the  symptoms,  and  they 
are  not  prevented  by  previous  section  of  the  spinal 
cord  (to  check  ascending  nervous  impulses).  It 
seemxS  clear,  then,  that  there  is  a  chemical  poison  at 
work,  probably  some  product  of  autolysis.  A  com- 
paratively small  loss  of  blood,  that  would  not 
incommode  a  normal  animal,  brings  on  severe  collapse 
under  these  circumstances. 

It  is  well  known  that  extensive  muscle  injuries 
often  gave  rise  to  shock  in  the  war,  and  that  early 
amputation  might  save  the  patient's  life.  Too  much 
importance  must  not  be  attached  to  this,  because  it 
has  slowly  become  recognized  that  gas-gangrene 
infection  was  common  and  early,  produced  shock- 
like symptoms,  and  specially  affected  damaged 
muscle. 

\Miilst  it  is  admitted  that  absorption  of  products 
of  autolysis  after  crushing  may  be  a  contributor^^ 
cause  of  the  clinical  picture  we  know  as  shock,  it 
does  not  seem  possible  that  this  can  be  the  main 
factor.  Patients  may  exhibit  the  m.ost  typical 
symptoms,  leading  to  fall  of  blood-pressure  and 
death,  after  a  gunshot  wound  of  the  abdomen,  a 
Wertheim  hysterectomy,  or  an  amputation  at  the 
hip-joint,  but  in  none  of  these  is  there  much  oppor- 
tunity for  absorption  of  crush-products.  Crile  some 
3'ears  ago  crossed  the  circulation  of  two  dogs  by 
leading  the  carotid  arteries  and  jugular  veins  of  one 
to  the  other,  and  found  that  signs  of  shock  were  only 
induced  in  the  traumatized  animal.     Lindsay  and  I 


SURGICAL    SHOCK  91 

injected  lo  ex.  of  the  blood  of  a  wounded  man,  just 
dead  of  shock,  into  a  rabbit,  which  was  none  the 
worse  for  it,  though  lo  c.c.  is  a  large  dose  for  an 
animal  of  that  weight. 

Dale  and  Laidlaw  show  that  a  condition  resembling 
shock  may  be  induced  in  animals  by  poisoning  with 
histamine.  There  is  a  fall  of  blood-pressure  and  a 
concentration  of  the  total  blood-volume.  The 
reduced  pressure  is  not  due  to  any  failure  of  the 
heart  or  relaxation  of  the  arteries — indeed,  the 
arteries  are  contracted — but  to  a  paralytic  dilatation 
of  the  capillaries,  so  that  much  of  the  blood  is  with- 
drawn from  the  functioning  circulation  and  pooled, 
as  it  were,  in  a  backwater.  The  limbs  swell  in  a 
plethysmograph  and  the  intestines  are  reddened. 
The  red-cell-count  maj^  rise  to  13  million,  and  haemo- 
globin 140  per  cent.  The  total  blood- volume  by 
the  '  vital-red '  method  is  greatly  reduced.  Local 
application  of  histamine  to  the  cat's  pancreas  shows 
flushing  and  oedema,  but  the  arteries  do  not  stand 
out. 

There  is  a  double  effect — a  stagnation  of  the  cor- 
puscles in  the  capillaries,  and  an  exudation  of  plasma 
from  the  capillaries  into  the  tissues.  In  fact,  the 
phenomena  closely  resemble  those  seen  in  inflam- 
mation. 

THEORIES     OF     SHOCK. 

Most  of  the  older  theories  combated  in  previous 
editions  of  this  book  are  now  practically  abandoned. 

The  view  that  the  underlying  cause  of  all  the 
manifestations  is  an  exhaustion  paralysis  of  the  over- 
stimulated  vasomotor  centre  is  out  of  the  nmning, 


92  SURGICAL    SHOCK 

because  there  is  plenty  of  animal  evidence  that  this 
centre  can  still  give  good  reflexes  ;  also,  if  this  view 
were  correct,  there  onght  to  be  vasodilatation  of 
the  arteries,  which  is  not  true. 

The  acapnia  theory,  that  shock  is  due  to  loss  of 
carbon  dioxide,  fails,  because  there  is  no  evidence 
that  such  loss  occurs  in  human  cases.  ^ly  analyses 
showed  a  normal  blood-content  of  carbon  dioxide 
even  in  fatal  shock.  Also,  shock  can  develop  when 
the  patient  is  being  given  ether  from  Clover's  inhaler. 
Further,  re-breathing,  or  inhalation  of  COo,  does  not 
reheve  the  condition. 

Exhaustion  of  the  suprarenal  glands  will  not 
explain  the  fall  of  blood-pressure,  because,  as  I  have 
shown,  in  patients  dead  of  shock  the  glands  still 
contain  plenty  of  adrenalin.  Stewart  and  Rogoff 
find  that  during  the  onset  of  shock  in  animals  there 
is  no  change  in  the  adrenalin  output  in  the  suprarenal 
veins.  Bedford,  on  the  other  hand,  beheves  that 
there  is  a  slight  increase  in  the  output,  but  of  slow 
development. 

During  the  war  several  observers  have  expressed 
the  opinion  that  a  main  factor  in  shock  is  fat- 
embohsm.  They  declare  that  a  similar  clinical 
picture  can  be  produced  by  injecting  fat  globules 
into  the  circulation  ;  and  also,  that  in  patients  dead 
of  shock,  fatty  droplets  may  be  found  in  the  capillary 
blood  of  the  lungs  and  brain.  The  theory  cannot 
be  accepted.  It  is  unreasonable  to  suppose  that  fat- 
embohsm  will  occur  after  a  gunshot  injury  of  the 
abdomen,  or  during  such  a  dangerous  operation  as 
Wertheim's    hysterectomy    or    amputation    at    the 


SURGICAL    SHOCK  98 

hip-joint.  Blood  normally  contains  visible  fat  in 
animals  (McKibben).  My  own  blood,  drawn  for 
purposes  of  group  scrum  testing  in  France,  was  full 
of  fat. 

As  already  mentioned,  some  believe  that  intoxica- 
tion wdth  crush-products  from  the  muscles  is  the 
cause  of  shock.  Reasons  were  given  for  allowing 
that  this  may  be  an  element  in  some  cases,  but  that 
it  is  not  the  main  factor. 

According  to  Roger,  it  is  to  an  inhibition  or  fatigue 
of  the  nerve-cells,  first  in  the  bulbar  centres  and  later 
throughout  the  brain  and  spinal  cord,  and  invoh-ing 
at  length  all  the  cells  of  the  body,  that  we  must  look 
as  the  basis  for  the  phenomena  of  shock.  Guthrie, 
and  also  Crile,  have  put  forward  similar  theories. 
Crile  demonstrates  changes  in  the  cells  of  the  liver 
and  adrenals  as  well  as  in  the  brain.  He  believes 
that  the  cause  of  the  breakdown  of  the  cells  is  an 
intracellular  acidosis. 

The  conception  is  somewhat  vague.  By  the 
study  of  the  Nissl  granules  we  have  a  fairly  deli- 
cate method  of  estimating  the  functional  activity  of 
various  groups  of  nerve-cells.  Although  the  sensory 
nuclei  of  the  brain  are  gravely  affected,  and  some 
other  important  nuclei  and  cell-groups,  such  as  the 
Purkinje  cells  of  the  cerebellum,  Deiters'  nucleus, 
and  the  vagus  nucleus,  may  show  less  extensive 
changes,  yet  the  bulk  of  the  ner\'e-cells  in  the 
brain  and  cord  are  unaltered,  unless  the  patient 
survives  more  than  a  day,  or  when  there  has  been 
much  loss  of  blood,  when  all  the  brain-cells  suffer. 
The  direct  evidence  for  the  theory  is  therefore  very 
shadowy. 


94  SURGICAL    SHOCK 

It  may  prove  that  our  problems  may  be  solved 
for  us  by  the  more  recent  conception  that  in  shock 
a  great  deal  of  the  circulating  blood  is  pooled  in  a 
backwater  in  the  dilated  capillaries,  and  that  much 
of  the  plasma  escapes  into  the  tissues  ;  but  here 
again  there  are  grave  difficulties.  If  we  accept  this 
view,  how  shall  we  explain  the  pallor  of  the  skin 
and  hps,  the  inconstancy  of  the  raised  red-cell-count 
in  the  capillaries,  and  the  rarity  of  supranormal  red- 
cell-counts  and  haemoglobin  estimations  ?  Dale's 
picture  of  the  animal  dead  of  histamine  poisoning, 
with  all  its  organs  in  a  state  resembling  inflamma- 
tion, is  quite  unlike  the  pallid  appearance  of  a  man 
dead  of  shock.  These  difficulties  may  largely  be 
met  if  the  evidence  is  confirmed  that  much  of  the 
blood  is  stagnant  in  the  visceral  and  muscle 
capillaries,  on  account  of  failure  of  the  vis  a  tergo, 
or  an  active  dilatation  of  the  capillaries  themselves. 

I  do  not  believe  that  we  possess  sufficient  informa- 
tion just  at  present  to  justify  us  in  theorizing.  As 
Sherlock  Holmes  used  to  repeat,  it  is  wrong  to  draw 
conclusions  before  you  have  collected  all  your  facts- 
One  suggestion  may,  however,  be  ventured.  The 
fall  in  blood-pressure  may  be  due  in  part  to  loss  of 
muscular  tone  in  the  voluntary  muscles  ;  this  loss 
of  tone  in  its  turn  may  be  accounted  for  by  the 
exhaustion  of  the  sensory  nerve-cells  in  the  brain- 
stem. 

There  is  a  condition  well  known  to  experimental 
physiologists  called  spinal  shock.  In  monkeys,  and 
to  a  much  less  extent  in  cats  and  dogs,  a  high  tran- 
section  of   the   spinal   cord   is   followed   by   grave 


SURGICAL    SHOCK  95 

interference  with  the  functions  of  the  cord  distal 
to  the  section.  For  a  period  varying  from  hours  to 
days  no  reflexes  can  be  obtained,  muscular  tone  is 
abolished,  and  the  blood-pressure  falls.  In  human 
surgery  we  see  the  like  condition  in  spinal  concussion, 
in  which,  after  a  blow  on  the  back,  sensation, 
voluntary  power  of  movement,  and  reflexes  may  be 
abolished,  but  after  a  day  or  two  are  all  restored  to 
normal. 

Professor  Sherrington  has  made  some  important 
investigations  into  the  nature  of  spinal  shock.  In 
the  first  place,  he  shows  that  it  only  affects  those 
segments  of  the  cord  distal  to  the  lesion  ;  thus,  after 
an  upper  dorsal  transection  the  cervical  segments 
are  not  in  shock.  Secondly,  he  shows  that  after 
recovery  has  taken  place,  a  second  transection — for 
instance,  in  the  middorsal  region — will  not  repro- 
duce the  signs  of  spinal  shock  :  proving  it  was  due 
to  the  withdrawal  of  influences  descending  from 
the  brain  or  brain-stem.  Again,  cutting  across  the 
mesencephalon,  above  the  pons,  does  not  induce 
spinal  shock.  Therefore  the  impulses  preventing 
it  must  have  com.e  down  from  the  region  of  the 
fourth  ventricle.  We  also  know  that  from  this 
same  region,  and  in  particular  from  the  central 
nuclei  of  the  vestibular  nerve,  descend  the  impulses 
which  give  rise  to  excess  of  muscular  tone.  A 
transection  of  the  mid-brain  causes  decerebrate 
rigidity  of  the  limbs  ;  a  second  transection  below 
the  medulla  abolishes  the  excess  of  tone.  On  this 
subject  the  writings  of  Sherrington  and  of  Thiele 
may  be  consulted. 


96  SURGICAL    SHOCK 

F.  H.  Pike,  of  Columbia  University,  has  latel}' 
published  a  very  important  research  on  spinal  shock, 
with  particular  reference  to  the  blood-pressure.  He 
shows  that  there  is  a  certain  residual  blood-pressure, 
about  33  mm.  of  mercury,  even  after  removal  of  the 
brain,  provided  that  the  cord  is  left  intact,  and  that 
sensory  stimuli  will  raise  this  pressure  reflexly. 
When  the  cord  is  totally  removed  there  is  a  very 
great  fall  of  pressure.  Apart  from  removal  of  the 
cord,  curare  produces  a  considerable  reduction  of 
blood-pressure,  both  in  normal  and  in  spinal  animals. 
This  curare  effect  is  not  due  to  any  action  on  the 
vessels,  but  to  the  abolition  of  tone  of  the  voluntary 
muscles.  This  is  in  accord  with  the  results  of  other 
workers. 

Again,  it  is  known  that  a  high  intraspinal  anaes- 
thesia induced  in  m.an  by  stovaine  or  some  similar 
drug  may  give  rise  to  a  dangerous  fall  of  blood- 
pressure  b\^  paralyzing  the  lower  part  of  the  body. 
This  risk  led  many  surgeons,  myself  amongst  the 
number,  to  abandon  the  use  of  intraspinal  anaesthesia 
at  casualty  clearing  stations. 

Do  we  not  here  find  another  clue  to  our  problem  ? 
The  nuclei  which  are  responsible  for  maintaining 
muscular  tone  are  the  very  ones  that  have  been 
shown  to  suffer  the  loss  of  their  Xissl  granules. 
The  patient  who  is  suffering  from  shock  is  usually 
found  Ipng  in  a  state  of  complete  muscular  relax- 
ation. Loss  of  tone  in  the  voluntary  muscles  will 
remove  the  support  which  they  naturally  give  to  the 
intramuscular  veins  and  capillaries,  and  in  a  lesser 
degree  to   the   intermuscular  veins.     Therefore  the 


SURGICAL    SHOCK  97 

blood-prcssurc  falls  and  the  cardiac  output  is  re- 
duced, in  spite  of  undiminished  power  of  the  heart 
muscle  and  contracted  arteries. 

It  may  be  objected  that  muscular  tone  is  reduced 
in  various  nervous  diseases  and  under  anaesthetics 
without  a  marked  fall  of  blood-pressure,  but  it  has 
to  be  remembered  that  in  the  nervous  affections  the 
onset  is  very  gradual  and  can  be  compensated,  and 
under  anaesthetics  there  is  stimulation  of  the  heart 
and  vasomotor  centre  to  counteract  the  loss  of  tone. 
Under  ether,  at  any  rate,  the  muscles  may  be  very 
vigorous,  as  rigidity  of  the  abdominal  wall  frequently 
reminds  us.  Chloroform,  of  course,  does  reduce  the 
blood-pressure  after  a  time. 

Without  venturing  to  formulate  a  cut-and-dried 
theory,  then,  one  may  suggest  that  the  nociceptive 
impulses  which  bring  about  surgical  shock  do  so  by 
inhibiting  or  paralyzing  the  important  nuclei  in  the 
region  of  the  fourth  ventricle  and  perhaps  in  the 
cerebellum,  which,  as  Sherrington  and  others  have 
shown,  are  continually  sending  impulses  down  the 
spinal  cord,  maintaining  its  functional  activity  and 
increasing  muscular  tone.  When  such  inhibition 
or  paralysis  takes  place,  the  functions  of  the  cord 
are  greatly  reduced,  tone  is  abolished,  and  there- 
fore, as  a  secondary  result,  the  blood-pressure  may 
fall.  The  respiratory  centre,  and  perhaps  even  the 
vasomotor  centre,  share  in  this  inhibition  or  paralysis ; 
this  is  a  very  different  conception  from  tliat  which 
takes  exhaustion  of  the  vasomotor  centre  to  be  the 
prime  cause  of  all  the  symptoms.  Death  is  due  to 
the   reduced   pressure   failing   to   propel   the   blood 

7 


98  SURGICAL    SHOCK 

through  the  capillaries  and  veins  ;  so  that  the  vis  a 
icrgo  is  no  longer  able  to  provide  a  proper  filling  for 
the  heart,  especially  as  the  feeble  respiratory  move- 
ments fail  to  exert  their  important  pumping  action. 

A  verj?"  striking  example  of  this  sequence  is  met 
with  in  what  is  called  '  the  knock-out  blow '  in 
pugilism,  or  rather,  one  of  such  blows.  A  vigorous 
drive  on  the  point  of  the  lower  jaw  in  a  line  from 
the  chin  to  the  condyles  is  transmitted  directly  to 
the  labyrinth  of  the  internal  ear,  and  by  way  of  the 
vestibular  nerve  impulses  reach  the  nuclei  of  which 
we  have  been  speaking.  As  a  result,  a  powerful 
athlete  is  immediately  reduced  to  a  mass  of  quivering, 
unstrung  flesh,  and  may  die  outright.  In  a  word, 
he  is  in  a  state  of  shock. 

As  a  result  of  a  moderate  fall  of  blood-pressure, 
there  is  a  much  more  marked  reduction  of  blood- 
flow.  Gesell  showed  that  a  fall  of  pressure  from  124 
to  84  mm.  Hg  in  the  cat  reduces  the  blood-flow  in  the 
submaxillary  gland  to  one-sixth.  Therefore,  before 
long  all  the  tissue-ceUs  of  the  body  are  suffering  from 
an  oxygen  famine,  and  soon  pass  beyond  recovery. 
The  starv^ed  cells  demand  a  local  capillary  dilata- 
tion, and  this  in  its  turn  withdraws  more  of  the 
circulating  blood  into  a  stagnant  backwater. 

PREVENTION  AND  TREATMENT  OF  SHOCK. 

It  is  to  be  feared  that  in  spite  of  aU  the  research 
of  workers,  young  and  old,  of  all  the  warring  nations, 
we  are  still  too  often  helpless  in  the  presence  of  grave 
shock.     Nevertheless,  real  progress  has  been  made. 

Fluids. — ^There  is  no  doubt  as  to  the  value,  slight 


SURGICAL    SHOCK  99 

but  definite,  of  giving  fluids.  Probably  potassium 
citrate  is  helpful,  by  keeping  the  acidosis  within 
bounds.  Saline  per  rectum  or  subcutaneously  is 
also  beneficial,  but  the  administration  should  not 
be  allowed  to  disturb  the  patient  too  much.  Tea  or 
coffee  may  help  as  nerve  foods. 

Wannth. — All  war  experience  agrees  that,  after  a 
serious  injury,  cold  much  aggravates  the  risks  to  life. 
The  patient  ought  therefore  to  be  kept  warm. 

Sleep  is  of  considerable  value.  It  is  well  known 
that  long  wakefulness  induces  changes  in  the  nerve- 
cells  similar  to  those  met  with  in  shock,  and  that 
after  sleep  Nissl  granules  are  restored  to  normal. 
Every  effort  should  therefore  be  put  forth  to  secure 
warmth,  comfort,  darkness,  and  quiet  for  the  shocked 
patient.  This  is  more  important  than  '  fussing '  him 
with  long-continued  sahne  injections.  Whether 
morphia  is  indicated  is  a  debatable  point.  Its  use 
is  strongly  advocated  by  Crile,  who  advises  repeated 
doses  every  hour  until  the  respirations  are  reduced 
to  twelve  per  minute.  I  have  seen  the  method  used 
with  some  success  in  casualty  clearing  stations.  In 
one  case  suffering  from  compound  fractured  femur, 
under  the  care  of  Lieut. -Colonel  Dun,  the  patient 
had  been  given  over  2  grains  of  morphia  in  four 
hours  ;  he  was  awake,  free  from  pain,  the  pulse  had 
improved,  and  the  pupils  were  not  contracted.  He 
made  a  good  recover}'.  On  the  other  hand,  it  has 
been  maintained  that  the  reduced  respirations  will 
interfere  with  oxidation  and  so  increase  the  acidosis. 
This  seems  too  theoretical  a  reason  to  stand  in  the 
way.     The   moderate  use   of  morphia   in  shock   is 


100  SURGICAL    SHOCK 

certainly  merciful  and  probably  restorative,  at  any 
rate  in  cases  where  pain  is  extreme.  It  ought  not 
to  be  used  if  the  nails  are  blue. 

Drugs. — Adrenalin  is  dangerous.  Strychnine  is 
certainly  useless  and  possibly  dangerous,  as  Crile 
and  Lockhart-Mummery  long  ago  pointed  out. 
Alcohol  may  give  a  little  Dutch  courage  to  patients 
with  syncope,  but  in  shock  it  does  nothing  but  harm, 
especially  after  ether  or  chloroform  has  been  ad- 
ministered, because  in  that  case  it  does  not  even 
produce  the  brief  rise  of  blood-pressure  that  precedes 
the  longer  fall.  Pituitary  extract  was  given  on  the 
theory  that  shock  was  due  to  arterial  dilatation  ; 
the  theory  is  erroneous,  and  the  drug  is  probably 
useless  unless  there  is  an  element  of  intestinal  para- 
lysis in  the  case  ;  for  that  condition  it  is  our  best 
remedy.  Camphor  is  well  spoken  of  by  some  ;  I 
have  little  experience  of  it. 

It  wiU  be  replied  to  the  above  rather  sweeping 
condemnation  that  in  such-and-such  a  remembered 
incident,  a  patient  very  bad  on  the  operation-table 
was  given  strychnine,  or  brandy,  or  pituitary,  and 
the  pulse  soon  became  better.  To  which  the  answer 
is,  in  the  first  place,  that  many  remedies  produce 
a  brief  stimulation  of  the  circulation,  followed  by 
a  prolonged  depression;  and  next,  that  it  is  not 
universally  known  how  common  it  is  for  patients' 
pulses  to  fail  during  the  later  stages  of  an  operation, 
and  then  to  improve  greatly,  apart  from  any  drug 
treatment,  during  the  stitching-up  and  application 
of  dressings.  It  is  this  phenomenon  which  has 
given  a  fictitious  reputation  to  strychnine  and  the 


SURGICAL    SHOCK  101 

rest    in    the   treatment    of  shock  during  an  opera- 
tion. 

One  is  almost  compelled,  however,  to  give  some 
hypodermic  remedy  to  pacify  patients,  friends,  and 
nurses.  I  believe  that  digitalin  is  useful,  both  on 
theoretical  grounds  as  a  circulatory  stimulant,  and 
as  a  matter  of  experience. 

Transfusion. — Intravenous  saline  transfusion,  es- 
pecially in  large  quantity,  has  a  definite  but  very 
small  and  transient  beneficial  effect.  It  may  tide 
the  patient  over  a  brief  period,  such  as  a  critical 
operation.     In  a  few  hours  its  value  is  all  gone. 

In  Bayliss's  gum-saline  transfusion  (6  per  cent  gum- 
acacia  in  normal  saline)  we  have  a  remedy  of  proved 
value  for  cases  of  severe  loss  of  blood  and  also  for 
shock,  but  it  must  be  given  early,  before  the  tissue- 
cells  have  suffered  from  the  failure  of  the  circulation. 
A  normal  quantity  to  introduce  is  about  a  pint, 
allowing  fifteen  minutes  for  it  to  run  in.  Both  in 
animals  and  man  it  gives  much  more  lasting  results 
than  salines,  because  the  gum,  being  a  colloid  sub- 
stance, does  not  readily  diffuse  out  through  the 
capiUary  endothelium  into  the  tissues.  Gum  is  not 
such  an  unphysiological  substance  as  might  be 
supposed  ;  it  consists  of  anhydrides  of  galactose  and 
arabinose  (a  pentose  sugar).  It  is  certainly  harm- 
less in  itself.  It  lasts  longer  than  twenty-four  hours, 
but  less  than  three  weeks,  in  the  circulation. 

Erlanger  and  Gasser,  finding  little  or  no  benefit 
from  Bayliss's  gum  in  shocked  animals,  advise  the 
use  of  a  25  per  cent  gum  in  18  per  cent  dextrose,  but 
it  is  very  difficult  to  handle  such  a  viscid  solution, 
and  the  results  in  man  are  not  very  convincing. 


102  SURGICAL    SHOCK 

Gum-transfusion,  though  convenient  and  valuable, 
has  one  defect  :  the  fluid  introduced  acts  merely 
as  a  passenger ;  it  cannot  give  any  active  help 
to  the  oxygen-starv^ed  tissue-cells.  Therefore  it  is 
inferior  both  theoretically  and  in  practice  to  blood- 
transfusion.  The  experience  of  the  war  has  con- 
vinced everj^body  who  saw  it  used  to  any  extent  that 
this  is  the  best  remedial  measure  in  our  armamen- 
tarium, certainly  for  the  shock-haemorrhage  complex, 
and  probably  for  pure  shock.  Admittedly  it  is 
difficult  to  get  donors  just  when  required ;  ad- 
mittedly the  technique  is  complicated ;  but  if  a 
method  is  the  best,  we  ought  to  use  it. 

PREVENTION  OF  SHOCK  DURING 
OPERATIONS. 

•  It  is  difficult  to  produce  shock  in  an  over- 
transfused  animal,  and  possibly  a  prehminary  blood- 
or  gum-transfusion  may  be  of  value.  There  is  no 
doubt  that  warmth,  gentleness  in  operating,  clean- 
cutting  instead  of  the  pulling  and  tearing  that  Crile 
designates  as  'carnivorous  surgery',  and  attention 
to  haemostasis,  are  all  important. 

The  nitrous-oxide-oxygen  mixture  is  far  superior 
to  ether  or  chloroform  in  protecting  the  nerve-ceUs 
against  the  functional  and  histological  changes 
induced  by  a  bombardment  of  painful  or  potentially 
painful  (nociceptive)  impulses.  Spinal  anaesthesia 
did  not  come  well  through  the  ordeal  of  war  ;  the 
abohtion  of  muscular  tone  in  the  lower  parts  of  the 
body  allows  a  dangerous  fall  of  blood-pressure. 
Crile's    anoci-association    methods    are    promising ; 


SURGICAL    SHOCK  103 

the  idea  is  to  block  all  the  nociceptive  messages 
derived  from  the  operated  area  by  first  exposing 
and  injecting  the  main  nerve-trunks  with  novocain. 
For  peritoneal-covered  surfaces  the  longer-lasting 
quinine-urea-hydrochloride  is  used.  For  some  years 
I  have  mopped  all  suture-lines  in  gastro-intestinal 
surgery  with  this  solution,  and  dipped  the  suture  in 
it.  This  greatly  reduces  reflex  gastro-intestinal 
paralysis  above  the  part  operated  on,  and  in  conse- 
quence the  patient  does  not  suffer  to  any  extent 
from  *  gas-pains  ',  as  the  Americans  expressively  call 
them.  The  comfort  after  a  big  abdominal  operation 
is  often  most  remarkable. 

After  a  big  smash  of  a  limb,  it  is  probably  wise  to 
keep  the  tourniquet  on  until  the  limb  is  amputated, 
so  as  to  avoid  absorption  of  toxic  crush-products. 

INTRAVENOUS     SALINE     TRANSFUSION. 

During  the  past  few  3'ear:^,  the  scope  for'  this 
proceeding  has  been  enlarged  considerably  by  the 
introduction  of  the  intravenous  methods  of  giving  sal- 
varsan  for  SN^phihs,  or  ether  as  a  general  anaesthetic  : 
and  Rogers  reports  great  benefit  from  the  injection  of 
hypertonic  saline  solutions  for  cholera.  The  success 
which  has  attended  its  use  in  the  :  treatment  of 
shock,  and  especially  of  collapse  after  haemorrhage, 
has  caused  it  to  be  used  more  and  more  extensively 
for  these  conditions.  At  the  same  time,  some  ver}' 
serious  drawbacks,  in  a  degree  avoidable,  have  come 
to  light,  and  with  these  wg  must  now  deal. 

We  need  barely  mention  the  difficulty  of  finding 
and  introducing  the  cannula  into  the  vein,  the  danger 


104  SURGICAL    SHOCK 

of  injecting  air-bubbles,  and  the  necessity,  when  the 
solution  is  made  up  in  a  private  house,  of  using  cook- 
ing salt,  and  not  a  table  salt  diluted  with  farinaceous 
or  other  material.  More  care  is  necessary  than  is 
usually  taken  to  see  that  the  temperature  at  which 
the  fluid  enters  the  vein  is  correct  ;  that  of  the  saline 
in  the  funnel  may  be  many  degrees  higher,  especially 
at  first.  It  is  easy  to  let  the  solution  flow  over  the 
bulb  of  a  thermometer  before  introducing  the  cannula. 
Then,  again,  the  proper  strength  of  sodium  chloride 
(0'9  per  cent  ;  a  teaspoonful  and  a  half  to  the  pint) 
must  be  employed.  It  is  far  more  physiological  to 
use  Ringer's  fluid,  containing  calcium  and  potassium 
salts  as  well,  with  a  little  dextrose  added  to  act  as  a 
food-stuff.  Compressed  tablets  of  the  correct  com- 
position are  upon  the  m.arket.  This  fluid  approxi- 
mates more  nearly  to  that  of  plasma,  and  is  capable  of 
maintaining  the  life  and  activity  of  the  tissues  much 
longer,  than  simple  saline. 

There  are  two  dangers  which  may  follow  the  trans- 
fusion. The  first  depends  upon  the  water,  and  the 
second  upon  the  salt.  Wechselmann  in  Germany, 
and  Hort  and  Penfold  in  England,  have  pointed  out 
that  water  supposed  to  be  sterile  usually  produces 
shivering  and  fever  in  animals,  and  frequently  in 
man,  alter  intravenous  transfusion  or  subcutaneous 
injection.  In  Wechselmann' s  cases  this  was  usually 
due  to  actual  contamination  wdth  bacteria  during  the 
days  or  weeks  that  the  water  was  left  standing  after 
distillation.  The  English  observers  found  that 
although  water  just  distilled  and  collected  in  a  glass 
retort  produced  no  fever,  yet  within  a  few  days  after 


SURGICAL    SHOCK  105 

standing  in  scaled  sterile  vessels  it  acquired  the 
property  of  giving  rise  to  fever,  and  that  in  spite 
of  boiling  or  filtration  through  a  Bcrkefeld  filter 
immediately  before  use.  In  some  cases  the  tempera- 
ture was  high,  but  not  fatal  unless  quite  unsuitable 
injections  were  given. 

Another  danger  depends  on  the  salt  used.  The 
total  quantity  injected  ma}'  be  very  large — ten  grams 
or  more.  A  condition  of  hydrsemic  plethora  is  likely 
to  be  induced,  that  is,  a  dilution  and  increase  in  Die 
total  volume  of  the  blood.  As  Lazarus  Barlow  has 
shown,  the  specific  gravity  at  once  falls  (e.g.,  from 
1-064  to  i"054).  The  kidneys  and  l3^mph-channels 
promptly  excrete  the  excess  of  fluid,  and  in  many 
cases  overshoot  the  mark,  so  that  eventually  the 
specific  gravity  may  be  I'ody,  signifying  of  course 
that  the  blood  is  less  in  bulk  ar.d  more  concentrated 
than  it  was  before.  This  does  not  occur  if  the 
supply  of  fluid  is  kept  up  by  further  injections,  or 
saline  ^ven  by  the  bowel. 

If  the  kidneys  are  not  capable  of  excreting  the 
water  and  salt  quickly  enough,  some  degree  of  dropsy 
may  occur,  and  as  the  Grunbaums  have  pointed  out, 
this  may  take  the  form  of  fatal  oedema  of  the  lungs, 
which  has  frequently  been  described  as  following  saline 
transfusion,  especially  in  patients  with  nephritis.  The 
Griinbaums  consider  that  the  use  of  ether  as  an 
anaesthetic  helps  to  determine  the  occurrence  of  such 
pulmonary  oedema.  If  the  salt  solution  injected  is 
too  concentrated,  a  greater  degree  of  hydraemic 
plethora  is  induced,  and  the  risks  of  pulmonary 
oedema  are  increased  ;  naturally  it  is  more  likely  to 
occur  after  a  large  injection  than  a  small  one. 


106  SURGICAL    SHOCK 

These  unfavourable  possibilities  are  not  mentioned 
to  proscribe  the  use  of  saline  transfusion,  but  to  call 
attention  to  the  best  methods  of  avoiding  complica- 
tions. Of  the  last  eight  cases  in  which  it  has  been 
used  at  the  Bristol  Royal  Infirmary,  only  one  (a  case 
of  mesenteric  thrombosis)  died,  although  the  treat- 
ment is  reserv^ed  for  the  most  desperate  conditions, 
especially  h^emoiThage,  and  most  of  the  patients  were 
pulseless.  Neither  fever  nor  lung  complications  re- 
sulted, although  a  solution  which  had  been  standing 
was  used.  Several  of  the  patients,  however,  had 
fever  before  the  injection  began,  and  this  continued. 
Not  more  than  one  or  two  pints  were  used,  and  this 
was  followed  by  saline  per  rectum  in  most  instances. 

To  obtain  the  best  results  and  the  fewest  fatalities, 
not  more  than  thirty  or  forty  ounces  of  freshly 
distilled  water,  collected  in  a  sterile  glass  vessel, 
should  be  injected.  In  this  a  powder  having  the 
composition  of  Ringer's  fluid,  with  dextrose,  should 
be  dissolved.  The  powder  must  be  sterilized  or  the 
solution  boiled.  The  transfusion  must  be  made 
slowly,  and  at  a  suitable  temperature  {ioo°  F.), 
and  it  should  be  followed  by  saline  injections  per 
rectum  to  avoid  the  reversal  of  the  effect.  If 
Bright's  disease  is  known  to  be  present,  the  treatment 
should  not  be  used. 

REFERENCES. 

Rendle  Short. — Brit.  Jour,  of  Surg.,    1919,    Jan.,  p.  402  ; 

Med.   Ann.,   1919,    1920,  Article  "  Shock  "  ;   Hunterian 

Lecture,  Lancet,  1914,  i,  p.  371. 
Dale  and  Laidlaw. — Jour,  of  Physiol.,  1919,  lii,  355. 
Bayliss. — Iniravenoiis  Injection  in  Wound  Shock,  1918. 


107 


CHAPTER    V. 

RECENT     WORK     ON     THE    FUNCTIONS 

OF     THE 
STOMACH     AND     INTESTINES. 

MOVEMENTS  OF  THE  STOMACH  —  MOVEMENTS  OF  THE 
INTESTINE — SENSATION  IN  THE  ALIMENTARY  CANAL — 
VARIATIONS  IN  THE  HYDROCHLORIC  ACID  OF  THE  STOMACH 
THE  PHYSIOLOGY  OF  GASTROJEJUNOSTOMY ABSORP- 
TION   IN    THE    COLON. 

IT  is  true  in  a  very  special  degree  concerning  the 
stomach  and  intestines,  that  we  have  learned 
much  about  the  physiology  of  animals,  but  little  of 
the  functions  of  man.  What  is  particularly  needed 
at  the  present  time  for  a  better  understandin.i: 
of  the  processes  that  take  place  in  the  alimentary 
canal  is  more  study  of  human  material.  Happily, 
during  the  past  ten  years  a  considerable  amount  of 
knowledge  has  been  gained,  but  much  still  remains 
obscure  ;  and  especially  wc  need  information  as  to 
the  relations  between  the  functions  of  one  part  of 
the  canal  and  another. 

MOVEMENTS  OF  THE  STOMACH. 

There  are  several  methods  of  studying  these  in 
man.  One  is  by  examining  with  the  x  rays  after 
giving  a  barium  (or  bismuth)  meal.  Watching  with 
the  fluorescent  screen  is  more  informing  than  taking 
plates.     Or,  one  may  pass  a  stomach  tube  at  intervals 


108  FUNCTIONS    OF    THE 

and  draw  off  the  contents  until  the  viscus  is  empty. 
Or,  a  rubber  ball  and  tube  (hke  that  often  used 
by  photographers  to  release  the  shutter)  may  be 
swallowed,  and  the  upper  end  of  the  tube  attached 
to  Marey's  tambour.  J^Iany  valuable  observations 
have  been  made  by  this  method  by  Carlson  in 
America. 

The  stomach  consists  of  two  distinct  parts,  which 
behave  quite  differently  during  digestion.  The  car- 
diac end  and  the  greater  part  of  the  body  form  an 
oval  reservoir  King  vertically,  with  a  well-marked 
angular  ring  separating  it  off  from  the  horizontal  or 
ascending  narrow  tubular  pyloric  antrum.  After 
death,  or  under  an  anaesthetic,  this  distinction  is  lost, 
but  it  is  often  seen  in  formalin-hardened  bodies. 
Just  after  a  meal,  the  greater  curvature  forms  the 
lowest  point,  and  in  men  while  standing  it  falls  a 
few  centimetres  below  the  umbilicus.  Later,  as  the 
stomach  shortens,  the  pylorus  becomes  the  lowest 
point. 

After  an  ordinary  meal,  movements  of  peristalsis 
start,  usually  about  the  middle  of  the  cardiac  reser- 
voir, and  advance  in  regular  waves  towards  the 
pylorus,  which  remains  tightly  closed.  In  man,  the 
waves  are  about  three  to  the  minute,  and  keep  on  so 
long  as  there  is  food  present.  The  consequence  is 
that  the  gastric  contents  become  thoroughly  mixed 
with  the  digestive  juices.  After  a  while,  when 
these  contents  are  sufficiently  acid,  the  pylorus 
begins  to  yield  momentarily  at  intervals,  and  to  let 
the  food  through  into  the  duodenum.  Whilst  acid 
is  present   on   the  far  side,   the  sphincter  remains 


STOMACH     AND    INTESTINES  109 

closed  ;  when  it  is  neutralized  it  opens  again.  Thus 
acid  in  the  stomach  opens  the  pylorus  ;  acid  in 
the  duodenum  closes  it.  This  goes  on  until  the 
stomach  is  empty.  Even  then  peristalsis  may  not 
cease  (Hurst),  but  the  pylorus  lies  open,  and  bile  and 
duodenal  contents  pass  in  and  out  without  causing 
any  discomfort.  The  stomach  normally  empties  in 
less  than  four  to  five  hours.  It  is  said  that  tickling 
the  ribs  may  lead  to  a  reflex  emptying  of  the  stomach, 
especially  about  three  hours  after  a  meal. 

The  effect  of  the  principal  foodstuffs  on  these 
movements  must  now  be  noticed.  Water  runs  out 
at  the  i^ylorus  almost  as  quickly  as  it  enters  by  the 
cardiac  orifice.  The  clotting  of  milk  is  probably 
designed  to  prevent  the  same  thing  happening ; 
otherwise  it  would  run  through  the  stomach  and 
duodenum  without  giving  the  pepsin  and  trypsin 
time  to  act  upon  it.  Carbohydrates  do  not  stay 
long  in  the  stomach  ;  fats  and  proteins,  however^ 
may  remain  for  several  hours.  In  a  normal  human 
stomach,  nothing  should  be  present  before  breakfast 
in  the  morning ;  if  there  is,  some  stasis  must  be 
occurring. 

A  number  of  investigators  at  the  Jefferson  Medical 
College,  Philadelphia,  have  made  some  interesting 
observations  on  the  time  taken  to  empty  the  stomach, 
and  the  total  acidity  developed,  after  partaking  of 
various  forms  of  meat.  They  find  that  there  are 
two  types  of  human  stomach,  the  rapid  and  the 
slow,  and  that  there  may  be  so  much  as  an  hour's, 
difference  in  the  emptying  time.  The  method 
employed  was  to  pass  a  stomach  tube  to  empty  the 


no  FUNCTIONS    OF    THE 

stomach,  then  take  the  meal  and  leave  the  tube  in 
place  until  the  washings  showed  that  everything 
had  passed  on  into  the  duodenum.  A  great  number 
of  experiments  were  made  on  many  subjects,  and 
the  meat  was  cooked  in  every  conceivable  way. 

Beef  takes  2-J  hours  to  leave  the  rapid  type  of 
stomach  ;  3J  hours  in  the  slow  type.  The  acidity 
rises  to  equal  120  c.c.  of  decinormal  alkali.  \^^ether 
the  meat  is  roast,  boiled,  or  corned,  the  times  and 
acidity  are  the  same.  Pork  takes  a  little  longer, 
and  the  acidity  is  rather  less  (on  account  of  the 
fat  mixed  in  with  the  meat  fibre).  Bacon  and  fried 
ham  digest  slowly — 4  to  4J  hours — and  the  acidity  is 
low.  Lamb  is  in  all  respects  much  the  same  as  beef. 
The  rapid  type  of  stomach  deals  with  eggs,  however 
cooked,  in  2  J  hours,  the  slow  type  in  3  hours.  The 
acidity  only  reaches  80.  If  the  eg§  is  cooked  with 
fat,  the  time  is  a  little  longer.  Raw  egg-white  is  out 
of  the  stomach  in  ij  hours. 

Emotion  hinders  peristalsis.  Excitable  cats, 
especially  males,  often  show  no  movements  for  a 
long  time  after  being  tied  down  ;  Cannon  did  most 
of  his  work  with  placid  elderly  female  cats.  Fever, 
such  as  distemper  in  dogs,  also  diminishes  the  move- 
ments ;  in  fact  food  may  lie  all  day  without  mo\'ing. 
There  is  great  delay  after  abdominal  operations.  If 
the  jejunum  is  cut  across  near  the  upper  end  and 
then  sutured,  the  pylorus  remains  tightly  closed  for 
about  six  hours,  even  if  food  is  given. 

Sohd  pellets,  such  as  bismuth  pills  or  lead  shot,  are 
not  allowed  to  escape  readily,  and  a  bread  mixture, 
which  usually  began  to  pass  out  into  the  duodenum 


STOMACH     Ay})    INTESTINES  ill 

in  fifteen  minutes,  was  retained  for  forty  minutes 
when  the  pills  were  given  with  it.  This  probably 
occurs  when  hard  indigestible  articles  are  taken  as 
food,  and  the  powerful  peristalsis  against  a  spas- 
modically contracted  pylorus  causes  pain. 

Hyperchlorhydria  in  animals  induces  prolonged 
spasm  of  the  pylorus,  lasting  over  many  hours, 
because  the  acid  in  the  duodenum  takes  so  long 
being  neutralized. 

MOVEMENTS    OF    THE    INTESTINE. 

We  have  always  known  that  the  small  intestine  is 
continually  in  movement,  the  main  character  of  the 
movement  being  an  onward  sweeping  wave  called 
peristalsis,  carrying  the  bowel  contents  from  the 
stomach  to  the  colon.  Peristalsis  consists  of  a  wave 
of  relaxation  pursued  by  a  wave  of  constriction.  It 
is  controlled  by  a  purely  local  mechanism,  and  will 
go  on  after  all  nerves  have  been  severed,  or  even 
after  taking  the  intestines  right  out  of  the  body. 
After  cutting  the  bowel  across,  the  wave  is  stopped 
at  the  point  of  division.  Fortunately  for  the  practice 
of  end-to-end  anastomosis  of  the  intestines,  any 
bowel  contents  which  may  be  pushed  through  the 
junction  will  start  a  fresh  wave  of  peristalsis  on  the 
distal  side  of  the  union.  Though  the  movements  are 
not  dependent  on  nerv^es,  they  can  be  influenced  by 
the  central  nervous  system,  as  every  one  knows  who 
has  suffered  from  an  attack  of  '  exam-funk  diarrhoea '. 
The  vagus  stimulates  peristaltic  movements ;  the 
splanchnic  nerves  inhibit  them.  In  the  small  intestine 
peristalsis  is  normally  only  from  stomach  to  colon, 


112  FUNCTIONS    OF    THE 

and  a  bismuth  meal  makes  the  journey  in  about 
four  hours.  There  is  a  sort  of  pendulum  swing- 
swang  of  whole  loops  of  bowel  going  on  at  the  same 
time,  and  also  a  segmentation  movement,  breaking 
up  the  alimentary  contents  into  short  lengths.  In 
the  large  intestine  the  conditions  are  very  different, 
and  have  an  important  bearing  on  certain  operative 
procedures.  The  movements  in  man  may  be  studied 
by  skiagraphy  after  bismuth  meals  or  bismuth 
enemata,  and  by  observations  on  patients  who  have 
suffered  various  forms  of  colostomy,  ileosigmoid- 
ostomy,  and  exclusion  operations.  When  the  abdo- 
men is  opened,  intestinal  peristalsis  soon  comes  to 
an  end  on  account  of  the  rapid  loss  of  CO^  from  its 
walls.  Saline  solution  saturated  mth  CO.,  restores 
the  movements  to  normal. 

In  the  caecum  and  the  ascending,  transverse, 
descending,  and  pelvic  portions  of  the  colon,  the 
motor  functions  are  involuntary,  as  in  the  small 
intestine,  but  with  some  striking  differences.  The 
food  residue  does  not  travel  at  a  slow  regular  rate 
of  progress  through  the  large  intestine.  It  lingers 
in  particular  locaUties,  such  as  the  caecum  and 
ascending  colon,  the  middle  of  the  transverse  colon, 
the  pelvic  colon,  and  the  rectum,  for  hours  at  a  time, 
and  although  it  has  been  denied,  it  is  certain  that 
antiperistalsis  occurs.  In  the  small  intestine  anti- 
peristalsis  is  rare  and  pathological.  Three  or  four 
times  a  day,  especially  by  a  gastrocohc  reflex  after 
taking  food,  the  intestinal  contents  are  carried  on- 
wards for  several  feet  by  massive  waves  of  peristalsis, 
of  which  the  patient  is  normally  quite  unconscious. 


STOMACH     AND    INTESTINES  113 

These  waves  have  been  witnessed  by  a  number  of 
observers.  Here  we  have  the  explanation  of  '  hen- 
teric  '  diarrhoea  immediately  following  a  meal,  and 
also  the  pain  after  food  met  with  by  some  sufferers 
from  chronic  constipation.  The  bismuth  meal 
normally  reaches  the  pelvic  colon  in  about  twenty- 
four  hours. 

The    existence    of    currents    of    antiperistalsis    is 
very    important     surgically.      Many     patients     on 
whom    ilcosigmoidostomy    (turning   the    ileum   into 
the  pelvic  colon  or  sigmoid)  has  been  performed  for 
growth  of  the  ascending  colon  have  suffered  great 
subsequent  discomfort  from  the  passage  of  gas  and 
f^ces  into  the  Wind  loop  of  colon,  from  the  opening 
into  the  sigmoid  up  into  the  descending  colon,  and 
so   round   towards   the   caecum.      In   some   cases   a 
second  operation  has  been  necessary.     In  all  ana- 
stomoses and  excisions   of  the  large  intestine   this 
physiological  factor  must   be  calculated  upon  and 
provided  for.     In  some  cases  an  appendicostomy  has 
been  performed  to  allow  flatus  to  escape  and  to  make 
lavage  possible,  but  this  is  not  very  effectual.     I  have 
on  many  occasions,  when  performing  an  end-to-end 
anastomosis  of  the  ileum  to  the  pelvic  colon  to  relieve 
obstructive  conditions,  exteriorized  the  distal  stump 
of  the  ileum  a  few  inches  from  the  ileocaecal  sphincter. 
More  than  once,  especially  after  giving  an  aperient, 
the  contents  of  the  ileum  having  entered  the  pelvic 
colon  have  been  carried  by  antiperistalsis  round  the 
descending,  transverse,  and  ascending  colons,  forced 
the  valve,  and  discharged  on  the  surface  through  the 
stump  of  ileum.     In  most  people  antiperistalsis  is  not 


114  FUNCTIONS    OF    THE 


« 


so  strong  as  this,  but  it  can  be  seen  by  barium  skia- 
graphy sweeping  the  ileal  efflux  that  has  just  entered 
the  pelvic  colon,  up  as  far  as  the  splenic  flexure. 
After  six  months  I  close  the  ileal  safety-valve. 

We  are  coming  to  look  upon  the  stomach  and  intes- 
tines as  resembling  a  canal  system  with  lock-gates 
connected  by  telephone,  so  that  the  state  of  traffic  at 
one  lock  has  an  influence  upon  the  rate  at  which  boats 
are  allowed  through  the  locks  above  and  below. 
According  to  Keith,  there  are  seven  sphincters  guard- 
ing the  stomach  and  intestines,  besides  one  at  the 
junction  of  the  pharynx  and  oesophagus. 

1.  The  cardia,  at  the  junction  of  oesophagus  and 
stomach  ;  contains  a  special  tj^pe  of  muscle  called 
'  nodal  tissue'. 

2.  The  pylorus,  with  a  node  near  the  bile-duct. 

3.  The  duodenojejunal  flexure,  with  a  special 
nerve-supply. 

4.  The  ileoccBcal  '  valve '  with  a  long  tubular 
sphincter  just  above  it,  \\ith  a  special  nerve-supply 
from  the  vagus  and  splanchnics. 

5.  The  traiisverse  colic  sphincter,  just  below  the 
pylorus,  with  a  special  nerve-supply. 

6.  The  pelvirectal,  at  the  junction  of  the  pelvic 
colon  and  rectum. 

7.  The  antis. 

The  clinical  evidence  for  some  of  these  is  at  present 
slight  or  wanting,  but  concerning  four  or  five  there 
is  no  room  for  doubt. 

Hurst  has  recently  drawn  attention  to  the  functions 
of  the  ileoca^cal  sphincter,  which  guards  the  passage 
through  the  ileocaecal  '  valve',  and  delays  the  entry 


STOMACH    AND    INTESTINES  115 

of  the  contents  of  the  small  intestine  until  time  has 
been  allowed  for  proper  absorption  of  food-stuffs. 
Skiagraphy  after  a  barium  meal  shows  that  the 
vanguard  of  the  meal  reaches  the  caecum  in  four  to 
ftve  hours,  but  that  the  rearguard  is  held  up  by  the 
sphincter  until  about  nine  hours  after  the  food  was 
given.  In  cases  of  chronic  appendicitis  this  sphincter 
may  remain  tightly  contracted  for  as  long  as  twenty- 
four  hours— a  highly  significant  observation,  as  we 
shall  see.  Whenever  food  is  taken  into  the  stomach, 
the  ileocecal  sphincter  is  reflexly  inhibited,  and  the 
last  contents  of  the  ileum  pass  through. 

A  patient  was  recently  under  my  care  who  had 
had  the  cscum  opened  more  than  a  year  before  to 
cure  chronic  dysentery;  the  wall  of  the  caecum 
turned  inside  out  and  prolapsed  through  the  wound, 
exposing  the  ileocaecal  '  valve  '  on  the  surface  so  that 
its  action  could  easily  be  watched  (see  Frontispiece). 
It  was  quite  obvious  that  there  was  a  raised  ring  of 
muscle  constituting  a  sphincter  guarding  the  orifice, 
and  in  ordinary  this  sphincter  was  closed.  Within  a 
few  minutes  of  swallowing  food  the  sphincter  relaxed 
and  lay  quite  patulous  for  half  an  hour  or  more  after 
the  meal  had  been  finished,  and  jets  and  squirts  of 
orange  or  brown  Uquid  faeces  were  poured  through 
the  orifice,  a  teaspoonful  or  two  at  a  time,  every 
minute  or  so,  by  the  peristalsis  of  the  ileum.  This 
peristalsis  could  be  seen  going  on  through  the  thin 
everted  cscal  wall  all  the  time  ;  it  never  stopped 
even  when  the  valve  was  not  working.  There  were 
never  any  movements  of  the  caecum.  This  accords 
with  what  one  sees  on  screening  by  the  aid  of  x  rays  ; 


116  FUNCTIONS    OF    THE 

the  small  intestine  is  never  still,  but  the  large  intestine 
is  usually  quiescent.  Applying  acids  or  alkalies  to 
the  caecal  mucosa  did  not  alter  the  efflux  in  any  way. 
Pinching  the  caecal  wall  would  not  start  an  efflux,  but 
delayed  it  to  some  extent  when  it  was  already  active. 
Similar  cases  have  been  described  by  Macewen  and 
by  Rutherford.  In  Rutherford's  patient,  it  was 
observed  that  rectal  enemata  caused  great  activity 
of  the  ileum  with  opening  of  the  sphincter  ;  this 
did  not  obtain  in  my  case.  Thus  we  see  that  the 
ileocaecal  sphincter  is  reflexly  influenced  by  swallow- 
ing, and  perhaps  also  by  relaxation  of  the  colon 
sphincters  ;  indeed,  it  would  appear  that  the  passage 
of  food  into  the  stomach  is  the  normal  stimulus  for 
emptying  the  contents  of  the  distal  coils  of  the  ileum 
into  the  large  intestine.  The  efflux  did  not  entirely 
cease  when  no  food  was  being  taken,  but  one  might 
watch  for  half  an  hour  without  anything  occurring. 
Getting  up  and  walking  about  led  to  greater  ac- 
tivity.    There  was  no  great  loss  of  flesh. 

When  for  any  reason,  such  as  chronic  intestinal 
stasis,  bands  or  kinks,  growths  of  the  colon,  or 
chronic  appendicitis,  the  passage  through  from  the 
ileum  to  the  caecum  is  delayed,  there  is  also  delay, 
up  to  twelve  or  twenty-four  hours,  in  emptying  of 
the  stomach.  When  the  cause  of  irritation  or 
mechanical  block  in  the  ileocolic  region  is  removed, 
proper  emptying  of  the  stomach  in  the  normal  time 
is  soon  restored.  I  have  several  times  verified  this 
by  barium  skiagraphy  after  operation. 

The  ileocaecal  '  valve '  is  after  all  a  valve,  though 
its  principal  function  is  as  a  sphincter.     In  ordinary. 


STOMACH    AND     INTESTINES  117 

encmata  do  not  pass  it,  but  they  can  often  be  made 
to  do  so.  According  to  Case,  the  American  radio- 
grapher, incompetency  of  the  valve-action  is  a  fruit- 
ful source  of  abdominal  pain  and  other  symptoms, 
such  as  alternating  diarrhoea  and  constipation,  head- 
ache, and  arthritis,  which  may  be  due  to  toxemia. 
This'  view  is  shared  by  chnicians  (Kellogg,  etc.). 
The  incompetency  can  be  demonstrated  by  watching 
a   bismuth   enema   entering   the   ileum    under   the 

X  rays. 

Before  turning  from  the  motor  functions  of  the 
intestines,  another  experimental  observation  merits 
attention.     Pawlow  found  that  strong  stimulation  of 
any  sensory  nerves  might  cause,  in  dogs,  prolonged 
reflex    arrest    of    peristalsis.     Injury    of    abdominal 
viscera  was  particularly  Ukely  to  do  so.     Cannon  and 
Murphy  have  shown  that  even  gentle  manipulation 
of    the    bowel    causes    cessation    of    all    intestmal 
movements  for  three  hours  or  more.     The  condition 
might  be  described  as    'intestinal  shock'.     It  is  of 
great  surgical  importance.    Arrest  of  peristalsis,  quite 
apart  from  peritonitis,  occasionally  follows  strangu- 
lated hernia,  even  after  successful  operation  ;   it  may 
accompany  gall-stone  colic,  and  it  may  even  occur  as 
a  neurosis  or  in   association  with   organic  nervous 
disease.     Some    interesting    cases    are    reported    by 
Walton  in  a  discussion  of  the  subject.     The  milder 
degrees   of   the   condition   will   yield   to   turpentine 
enemata  and  to  saUne  purges,  but  there  are  instances 
in  which  all  drugs  are  vomited  and  the  block  seems 
to  be  too  high  for  enemata  to  act.     Here  we  may 
try  the  effect  of  physostigmine  (eserine)   salicylate, 


118  FUNCTIONS     OF    THE 

in  T^-gr.  doses,  given  hypodermically  every  four 
hours  for  six  doses.  Our  personal  experience  of  it 
is  favourable.  Walton  shows  by  a  chart  that  the 
evacuations  when  this  drug  is  given  after  abdominal 
operations  are  much  more  frequent  than  without  it. 
It  is  scarcely  at  all  aperient  in  health,  working  best 
when  the  local  nerve  gangha  in  the  intestine  are 
thrown  out  of  action.  It  is  of  course  an  old  and 
well-known  remedy,  acting  like  pilocarpine  by  stimu- 
lating the  nerve-endings  in  unstriped  muscle. 

Pituitary  extract  often  works  well  in  these  cases. 
It  is  better  than  ph^-sostigmine.  When  all  else  fails 
and  drastic  measures  are  needed  to  get  the  bowels 
to  work,  I  use  a  sort  of  triple  attack,  giving  two 
drops  of  croton  oil  by  mouth,  then  four  hours  after- 
wards an  alum  enema,  and  immediatelv  it  has  been 
injected  an  intramuscular  dose  of  pituitary.  This 
has  saved  four  or  five  cases  that  seemed  certain  to 
die  of  intestinal  paralysis  and  toxaemia. 

A  few  further  points  may  be  summarized  briefly. 

Intestinal  colic  is  due  to  some  interference  with  the 
normal  relation  between  the  wave  of  relaxation  and 
the  following  wave  of  contraction,  which  make  up 
normal  peristalsis. 

Ordinary  constipation  is  rarely  due  to  any  prolonga- 
tion of  the  normal  four  hours  taken  by  the  bismuth 
meal  to  pass  from  the  stomach  to  the  caecum.  Some- 
times the  delay  is  in  the  whole  length  of  the  colon  ; 
sometimes  the  fseces  reach  the  rectum  and  pelvic 
colon  in  good  time,  but  are  retained  there. 

There  is  a  condition  first  described  by  Sir 
Arbuthnot  Lane,  and  demonstrated  by  skiagraphy 


STOMACH     AND     INTESTINES  119 

by  Jordan,  called  chronic  intestinal  stasis.     I  used 
to  regard  it  as  a  rare  disease,  but  the  experience  of 
the  past  five  years  has  led  me  to  believe   that  it 
is  very  common,   but  often  overlooked  even  at  a 
laparotomv.     The  symptoms  form  an  extraordinary 
and   most"' perplexing  mimicry  of  other  and  better 
defined  ailments  which  give  rise  to  abdommal  pam, 
sometimes    associated    \vith    extreme    wastmg    or 
vomiting.     Some  of  my  cases  presented  the  chnical 
picture  of  gastric  ulcer  or  cancer,  others  of  chronic 
appendicitis,  others  of  cancer  of  the  colon,  and  in 
some  patients  the  symptoms  were  indefinite.   Men, 
women,  and  children  are  all  affected.    At  operation 
one  finds  great  distention  and  dropping  of  all  parts 
of   the   large  intestine,  especiaUy  the  cscum,  with 
adhesion-bands  holding  it  up.     One  of  these  bands 
is  caUed  Jackson's  pericolic  membrane.     The  appen- 
dix is  sometimes  pressed    into  service  to   act  as  a 
sling-band.     The    ileum   is   kinked   down    near   its 
termination    by  another   band.     The  duodenum  is 
greatly    dilated.     In   this  disease    the   whole  lock- 
gate  system   is  thoroughly  disorganized,   and  food 
may  he  for  a  day  or  longer  in  the  stomach.     It  is 
uncertain  how   far   all   this   is   due  to   mechanical 
obstruction    associated    with    dropping    of    all    the 
viscera  (the  kidney  often  drops  too),  or  whether  the 
nervous   reflexes   that    govern   the   sphincters— the 
telephone  insiaUation  of  the  lock-gate  system— have 
broken  down.     If  medical  treatment  (corsets,  belts, 
hquid  paraffin)    give   no   rehef,   operation   becomes 
necessary  in  the  worst  cases.     I  have  no  stereotyped 
procedure  ;   sometimes  it  is  sufficient  to  remove  the 


120  FUNCTIONS    OF    THE 

appendix  and  bands  ;  in  other  cases  c^coplication 
gives  a  good  result.  If  the  whole  colon  is  at  fault,  I 
perform  ileosigmoidostomy  (end-to-side  union  of  the 
ileum  with  the  pelvic  colon)  with  exteriorization  of 
the  distal  end  of  the  ileum  as  a  safety-valve  for  six 
months.  This  usually  (not  always)  effects  a  cure. 
It  is  too  soon  to  say  if  the  cure  is  permanent.  Ileo- 
sigmoidostomy without  a  safety-valve  does  more 
harm  than  good.  Sir  Arbuthnot  Lane  removes  the 
colon. 

The  movements  of  the  intestines  are  to  some  extent 
excited  by  a  hormone  produced  after  meals  in  the 
gastric  mucosa,  extracts  of  which,  during  digestion 
but  not  during  starvation,  will  excite  peristalsis 
when  given  by  intravenous  injection.  This  hormone 
is  also  stored  in  the  spleen.  Under  the  name  of 
'  hormonal '  it  has  been  introduced  into  medicine, 
and  is  of  value  both  for  cases  of  intestinal  paralysis 
after  operation,  and  also  for  chronic  constipation. 
A  single  injection  is  said  to  cure  an  old-standing 
constipation.  Unfortunately  it  is  not  always  active, 
and  there  have  been  a  few  fatalities,  probably  due 
to  extraneous  products  in  the  splenic  extract. 

As  we  have  seen,  the  small  intestines  are  in  a  state 
of  incessant  peristalsis.  If  for  any  reason  the  con- 
tents of  the  ileum  or  jejunum  are  unable  to  pass 
along,  dangerous  toxins  rapidly  accumulate.  If  a 
six-inch  length  of  a  dog's  small  intestine  is  isolated 
and  closed  at  each  end,  but  the  continuity  of  the 
bowel  is  restored  by  end-to-end  union,  in  spite  of 
the  fact  that  there  is  no  obstruction  a  fatal  toxaemia 
develops.     Within  forty-eight  hours  the  contents  of 


STOMACH    AND    INTESTINES  121 

the  closed  loop  are  highly  poisonous  to  a  normal 
dog,  causing  low  blood-pressure,  low  temperature, 
diarrhoea,  and  vomiting.  It  is  stated  that  the  toxin 
is  a  proteose  (Whipple,  etc.),  but  it  does  not  give 
rise  to  the  formation  of  any  antibodies  if  injected 
into  another  animal  in  repeated  increasing  doses. 
One  sees  this  condition  of  toxsemia  only  too  often 
when  the  small  intestine  is  blocked  by  peritonitis 
or  mechanical  obstruction.  It  is  the  authentic 
cause  of  a  good  many  deaths  after  wounds  or 
operation  that  are  wrongly  attributed  to  shock. 

SENSATION    in:  THE    ALIMENTARY    CANAL. 

In  his  recent  Goulstonian  Lecture,  Hurst  shows 
that  the  sensory  functions  of  the  viscera  are  much 
more  Umited  than  those  of  the  skin.  The  stomach 
and  intestine  do  not  possess  any  temperature  sense 
or  any  tactile  sense,  nor  is  cutting  painful,  but  puUing 
on  the  serous  coat  gives  rise  to  severe  pain.  The 
feeling  of  heat  or  cold  after  swallowing  Hquids  is 
appreciated  by  the  lower  end  of  the  oesophagus. 
Temperature  and  tactile  sense  are  quite  well  developed 
in  the  oesophagus,  and  locaUzation  is  very  accurate— 
seldom  more  than  an  inch  out. 

Hydrochloric  acid  may  be  poured  into  the  stomach, 
either  through  a  stomach-tube  or  a  gastrostomy 
wound,  without  producing  any  sensation  at  all, 
even  if  the  percentage  rises  to  0-5  or  even  2,  and  this 
is  true  also  in  cases  of  gastric  ulcer.  Alcohol  does 
excite  a  burning  feeUng.  Distention  of  the  stomach 
causes  a  sensation  of  fullness  ;  the  amount  of  dis- 
tention  necessary   depends   on   the   tonicity   of   the 


122  FUNCTIONS     OF    THE 

gastric  muscles.  Gastralgia,  whatever  its  cause,  is  due 
to  colicky,  irregular  contractions  of  the  muscle,  the 
pylorus  remaining  closed.  There  is  often  a  referred 
pain  or  tenderness  in  the  cutaneous  area  also.  The 
pain  of  peritonitis  is  probably  quite  a  different  thing. 
Sensation  in  the  intestine  corresponds  closely  in  its 
physiology  to  sensation  in  the  stomach.  The  anal 
canal,  however,  can  detect  thermal  and  tactile  stimuli. 

Carlson  has  recently  shovvU,  in  a  patient  with  a 
gastric  fistula,  that  the  sensation  which  we  call 
hunger  is  due  to  waves  of  peristalsis  in  the  empty 
stomach,  of  which  he  was  able  to  obtain  a  graphic 
record. 

Carlson  and  his  fellovr-vrorkers  have  made  some 
investigation  as  to  the  exact  cause  of  pain  in  gastric 
and  duodenal  ulcer.  In  dogs  with  a  duodenal  or 
pyloric  ulcer  induced  by  injecting  silver  nitrate  into 
the  mucosa,  the  peristalsis  of  the  stomach  (recorded 
by  the  baUoon  method)  is  excessive,  but  not  suffi- 
ciently so  to  account  for  the  pain  unless  the  nerves 
involved  in  the  ulcer  were  hyperexcitable  (Dundon). 
Carlson  points  out  that  the  hyperchlorhydria,  and 
the  rehef  given  by  alkalies,  are  usually  taken  to  mean 
that  the  pain  is  due  to  acid  irritation  of  the  exposed 
nerves  in  the  ulcer,  but  the  pain  is  discontinuous 
('  boring ')  in  character,  it  may  be  present  when  the 
HCl  is  subnormal  and  may  be  absent  when  there  is 
an  ulcer  present  with  hyperacidity,  and  alkahes  may 
relieve  pain  when  there  is  no  ulcer  or  no  hyperacidity. 
Putting  in  acid  does  not  increase  the  pain.  He  finds 
that  the  pains  synchronize  with  the  contractions  of 
the  stomach  as  registered  b}^  the  balloon  method,  or 


STOMACH     AND    INTESTINES  123 

watched  with  x  rays.  These  contractions  need  not 
be  excessive,  but  evidently  the  nerves  involved  in 
the  ulcer  are  hypersensitive. 

VARIATIONS    IN    THE    HYDROCHLORIC    ACID    OF 
THE     STOMACH. 

The  amount  of  acid  normally  present  as  free  HCl 
is  given  differently  by  different  physiologists,  some 
following  Topfer  and  rehing  on  amido-azo-benzol  as 
the  indicator,  others  using  the  more  accurate  but 
somewhat  tedious  method  of  Willcox.* 

It  has  been  customary'  to  take  the  normal  quantity 
of  free  HCl  as  o-2  per  cent,  but  Panton  and  Tidy 
and  other  workers  show  that  o-i  is  more  accurate, 
after  a  standard  test-meal.  The  total  gastric  acidity 
is  about  50  c.c.  of  decinormal  acid,  using  100  c.c. 
of  the  gastric  juice  to  make  the  test.  The  same 
quantity  of  juice  contains  enough  free  HCl  to 
neutralize  about  30  c.c.  of  decinormal  alkah.  The 
indicator  for  the  total  acidity  test  is  phenolphtha- 
lein,  and  for  the  free  HCl  either  Topfer's  reagent,  or 
phloroglucin  and  vanillin,    which  is  more  accurate. 

The  total  acidity  of  course  includes  lactic  acid  and 
any  other  fermentation  acids,  also  acid  phosphates, 
and  is  of  no  great  importance. 

An  interesting  self-regulating  mechanism  of  the 
acidity  of  the  gastric  juice  has  recently  been 
described.  As  secreted,  in  animals  and  man,  the 
hydrochloric  acid  is  as  much  as  0*5  per  cent,  but 
it  is  neutraUzed,  partly  by  food  and  partly  by  the 

*  Lancet f  1905,  i,  p.   1566. 


124  FUNCTIONS    OF    THE 

regurgitation  of  pancreatic  and  intestinal  juices, 
down  to  0-2  or  o*i  per  cent,  which  is  the  optimum, 
and  in  health  it  is  maintained  at  this  standard.  In 
hyperchlorhydria  this  regulation  breaks  down,  and 
the  acidity  approximates  to  0*5  per  cent. 

By  whichever  method  the  estimation  is  made,  it 
would  appear  that  diet  exercises  little  or  no  effect 
on  the  percentage  of  active  hydrochloric  acid, 
although  it  so  markedly  affects  the  pepsin.  Never- 
theless, the  percentage  of  acid  is  liable  to  change, 
and  the  changes  are  of  great  value  for  both  diagnosis 
and  treatment. 

Increased  relative  amount  of  HCl  is  particularly 
common  in  gastric  ulcer,  so  much  so  that  an  analysis 
of  a  test  meal  is  of  diagnostic  importance.  It  is 
also  seen  in  duodenal  ulcer,  and,  as  has  recently  been 
pointed  out,  in  many  other  affections  of  the  alimentary 
canal,  such  as  appendicitis.  It  is  probable  that  the 
cases  which  have  been  diagnosed  as  simple  hyper- 
chlorhydria have  usually  some  latent  disease,  if  not 
in  the  stomach  or  duodenum,  then  in  the  gall-bladder, 
kidney,  or  appendix,  and  removal  of  the  offending 
organ  will  cure  the  hyperchlorhydria.  The  sym- 
ptom characteristic  of  such  a  condition  is  '  hunger- 
pain  ',  that  is,  a  feeling  of  gnawing  of  the  stomach, 
which  may  be  only  a  discomfort  or  may  amount  to 
positive  pain  ;  it  occurs  two  or  three  hours  after  a 
meal,  and  is  relieved  by  food  or  alkaUes.  It  is  proba- 
bly due  to  the  spasmodic  contraction  of  the  pylorus 
set  up  by  the  long  persistence  of  the  acidity  on  the 
duodenal  side.  Another  view  is  that  it  is  caused 
by  incipient  self-digestion  of  the  stomach.     This  is 


STOMACH    AND    INTESTINES  125 

normally  guarded  against  by  an  anti pepsin  in  the 
mucous  membrane  reversing  the  activity  of  the 
gastric  juice,  but  the  continual  presence  of  an 
abnonnally  powerful  combination  of  acid  and  pepsin 
breaks  down  the  resistance,  just  as  is  seen  in  an 
exaggerated  degree  when  a  healthy  man  dies  suddenly 
during  the  process  of  digestion  ;  the  supply  of  anti- 
pepsin  fails  with  the  circulation,  and  a  big  hole  is 
dissolved  through  the  stomach  wall  post  mortem. 
It  is  highly  probable  that  hyperchlorhydria  is  a 
cause  as  well  as  a  consequence  of  gastric  ulcer ; 
certainly  it  determines  the  peculiar  punched-out 
character  which  the  typical  round  ulcer  assumes. 
It  is  significant  that  more  than  one  such  lesion  is 
occasionally  present,  as  though  the  excessively  acid 
juice  resulting  from  the  irritation  of  some  initial 
abrasion  not  only  had  deepened  that  lesion  into  an 
ulcer  but  had  determined  the  formation  of  others 
also.  It  is  again  significant  that  the  typical  punched- 
out  ulcer  occurs  just  where  the  acid  has  access,  and 
nowhere  else — at  the  lower  orifice  of  the  oesophagus, 
in  the  stomach,  and  in  the  first  two  inches  of  the 
duodenum,  while  in  the  jejunum  it  is  unknown 
except  at  the  site  of  a  previous  gastrojejunostomy 
opening,  and  not  even  then  unless  this  operation 
has  failed  to  cure  the  hj^perchlorhydria,  which  usually 
means  that  the  orifice  was  too  small  or  badly  placed. 
Another  evil  consequence  of  excessive  HCl  is  spasm 
of  the  pylorus,  which  may  lead  to  dilatation  of  the 
stomach.  A  curious  and  suggestive  symptom  is  pyrosis, 
a  periodical  copious  secretion  of  saUva,  probably  de- 
signed to  neutralize  the  acidity  when  swallowed. 


126  FU>XTIONS     OF    THE 

In  infants,  Willcox  and  R.  Miller  have  stated  that 
there  are  two  t\-pe5  of  dyspepsia  causing  pain, 
wasting,  vomiting,  and  constipation.  One  is  con- 
genital stenosis  of  the  pylorus,  in  which  the  HCl  is 
subnormal  but  the  pepsin  (which  may  be  conveniently 
tested  by  the  curdling  effect  on  milk)  is  excessive, 
and  mucin  is  also  in  excess.  The  other  is  '  acid 
dyspepsia  ',  in  which  the  HCl  is  excessive  and  the 
ferments  are  subnormal.  In  this  case  peristaltic 
waves  may  be  seen,  but  the  pyloric  tumour  is  not 
felt.  The  prognosis  is  very  much  better  than  in 
congenital  stenosis,  and  operation  is  not  needed  as 
it  so  often  is  in  the  more  serious  condition. 

Enough  has  been  said  to  show  that  hyperchlor- 
hydria  and  its  advertisement,  '  hunger-pain  ',  are 
more  than  an  inconvenience  to  the  patient  ;  they 
are  in  many  cases  the  consequence  and  in  other  cases 
the  precursor  of  serious  organic  mischief  which  may 
lead  to  dilated  stomach,  to  chronic  gastric  ulcer — 
which  in  its  turn  is  apt  to  become  malignant — 
or  to  an  abdominal  catastrophe  from  perforation  of 
the  stomach  or  duodenum. 

When  the  hv'perchlorhydria  is  not  associated  with, 
or  precedes,  ulceration  of  the  stomach  or  duodenum, 
the  appendix  or  gall-bladder  is  probably  at  fault. 
The  appendix,  for  instance,  may  show  adhesions  or 
stenosis. 

Sherren  found  the  appendix  normal  in  only  4  out 
of  65  cases  of  duodenal  ulcer,  and  5  out  of  41  cases 
of  gastric  ulcer.  Moynihan,  Paterson,  the  Mayos,  and 
others  have  shown  that  the  majority  of  the  gastric 
and  duodenal  ulcers  met  with  on  the  operation  table 


STOMACH    AND    INTESTINES  127 

are  associated  with  appendicitis.  The  sequence  is, 
first  appendicitis,  then  h3'perchlorhydria,  and  thirdly 
ulceration. 

Chronic  dyspepsia  is  often  the  only  complaint  in 
persons   who    have    no   hyperchlorhydria,    show    no 
local  symptoms  of  trouble  in  the  appendix,  but  are 
cured  by  removal  of  that  organ.     The  majority  of 
patients  diagnosed  as  gastric  ulcer  in  the  medical 
wards  of  a  hospital,  and  recovering  without  operation, 
in  all  probabihty  have  no  ulcer  at  all,  but  only  reflex 
gastric  symptoms  following  on  gall-stones,  movable 
kidney,  or  appendicitis.     In  20  per  cent  of  patients 
with  symptoms  of  gastric  ulcer  operated  on  at  the 
Bristol  Royal  Infirmary,  no  ulcer  was  found.     Why 
disease  of  the  appendix,  or  gall-bladder,  should  cause 
these   symptoms   it   is   difficult   to   decide.     It   can 
scarcely  be  due  to  toxic  absorption,  as  the  appendix 
may  be  quite  fibrotic.     Perhaps  the  simplest  explana- 
tion is  that  the  ileocaecal  sphincter  remains  tightly 
closed  and  produces  back-pressure.     In  other  cases 
there  may  be  irregular  gastric  peristalsis  and  hyper- 
chlorhydria as  a  nervous  reflex.     In  chronic  intes- 
tinal stasis  the  hydrochloric  acid  in  the  gastric  juice 
is  usually  deficient.     There  may  be  all  the  symptoms 
of  gastric  ulcer,  but  the  pain  usually  comes  on  soon 
after  food,  or  persists  all  the  time.     Reflex  closure 
of  the  pylorus  and  delayed  or  irregular  emptying 
appears  to  be  the  cause  of  the  symptoms  in  this  type 
of  case.     This  probably  accounts  for  the  dyspeptic 
pains   endured   by   so   many   persons   with   chronic 
appendicitis    whose    gastric    acidity    is    normal    or 
subnormal. 


128  FUNCTIONS     OF    THE 

The  treatment  of  hyperchlorhydria  is  as  follows. 
Medical  means  will  often  give  a  large  measure  of  re- 
lief. Taking  food,  and  especially  a  hard-boiled  e§^, 
when  the  pain  comes  on,  will  generally  abate  the  sym- 
ptoms. Alkalies  are  indicated,  especially  magnesia, 
which  has  two  advantages :  it  does  not  dissolve 
and  exert  all  its  effect  in  a  few  minutes,  and  it  does 
not  give  off  carbon  dioxide  as  the  carbonates  do. 
The  bismuth  lozenges  of  the  B.P.  are  convenient 
to  carry  and  very  successful  in  stopping  the  dis- 
comfort. We  will  barely  mention  such  useful 
measures  as  rest  in  bed,  milk  diet,  and  lavage.  On 
theoretical  grounds  Pawlow  recommends  fats  and 
oils  to  check  the  flow  of  the  gastric  juice.  These 
measures  are  of  course  not  applicable  in  the  presence 
of  an  acute  ulcer  causing  haemorrhage. 

If  these  means  are  not  successful,  it  is  very 
desirable  to  perform  laparotomy  and  to  explore  the 
stomach,  duodenum,  appendix,  kidney,  and  gall- 
bladder. If  gastric  or  duodenal  ulcer  is  present, 
gastrojejunostomy  is  of  course  indicated.  If  the 
ulcer  is  near  the  cardia,  it  is  probably  better  to 
excise  it.  If  no  abnormality  can  be  discovered  in 
either  stomach  or  duodenum  without  opening  into 
them  (which  is  seldom  if  ever  called  for),  it  may 
be  that  some  adhesions  or  kinking  of  the  appendix 
may  be  found,  and  removal  of  the  organ  will  effect 
a  cure  in  many  of  the  cases,  but  not  all.  It  is 
shown  by  Paterson,  the  Mayos,  Sherren,  and  others 
that  about  75  per  cent  of  the  many  hundreds 
of  cases  of  dyspepsia  without  ulceration  treated  by 
removal  of  the  appendix  are  cured.     Soltau  Fenwick 


STOMACH     AND    INTESTINES  129 

states  that  of  112  cases  of  hyperchlorhydria,  in  34 
the  stomach  and  duodenum  were  normal ;  in  22  of 
these  the  appendix  was  at  fault,  and  in  12  gall-stones 
were  present.  In  9  cases  appendix  trouble  compli- 
cated gastric  or  duodenal  ulcer.  In  66  patients  an 
ulcer  was  present  in  the  stomach  or  duodenum  ;  4 
of  these  were  malignant. 

It  is  a  remarkable  fact  that  severe  and  repeated 
haemorrhage  from  the  stomach  may  take  place  in  the 
absence  of  any  ulcer.  Out  of  seven  cases  recently 
operated  on  for  haematemesis  at  the  Bristol  Royal 
Infirmary,  in  only  two  was  an  ulcer  found.  A  con- 
dition of  universal  weeping  of  blood,  called  '  gastro- 
staxis ',  occurs  in  these  cases,  and  with  the 
gastroscope  the  mucous  membrane  may  be  seen  to 
ooze  blood  wherever  it  is  touched. 

THE    PHYSIOLOGY    OF    GASTROJEJUNOSTOMY. 

What  effect  is  produced  upon  the  functions  of  the 
alimentary  canal  by  the  operation  of  gastrojejuno- 
stomy ?  We  have  to  ask  :  (i)  Does  the  food  pass 
through  the  new  opening  or  by  the  pylorus  ?  (2) 
What  is  the  effect  upon  the  gastric  juice  ?  and  (3) 
What  is  the  effect  upon  the  absorption  of  proteins, 
fats,  and  carbohydrates  ? 

Some  light  has  been  thrown  upon  the  first  of  these 
questions  by  watching  with  the  x  rays  the  course 
taken  by  a  meal  containing  bismuth  oxide,  and  it 
would  appear,  as  might  have  been  expected,  that 
both  routes  are  followed,  unless  either  the  pylorus 
or  the  artificial  opening  is  or  becomes  greatty  nar- 
rowed. On  this  subject  the  writings  of  Cannon 
and  Gra}'  may  be  consulted. 

9 


130  FUNCTIONS    OF    THE 

The  former  used  cats  with  a  normal  stomach  on 
which  the  operation  had  been  performed,  and  natur- 
ally the  tendency  was  for  the  meal  to  take  the  pyloric 
route. 

Hartel*  has  made  a  study  by  this  means  of  22 
patients  operated  on  months  or  years  before.  About 
half  of  them,  including  those  in  which  pyloric  stenosis 
was  found  at  the  operation  to  be  severe,  emptied  only 
by  the  new  opening  ;  in  the  others  the  food  took 
both  directions.  In  one  case  it  appeared  to  pass  out 
only  by  the  pylorus. 

The  effect  upon  the  gastric  juice  is  nil  if  it  has 
previously  been  normal ;  if  hyperchlorhydria  was 
present,  an  efficient  gastrojejunostomy  appears 
invariably  to  restore  the  amount  of  acid  to  normal. 
Stenosis  of  the  opening  may  be  followed  by  a  return 
to  the  greater  acidity.  If  the  HCl  is  absent,  however, 
the  operation  will  seldom,  if  ever,  cause  it  to  appear. 

That  there  cannot  be  any  serious  loss  of  power  to 
digest  and  absorb  foodstuffs  is  shown  by  the  remark- 
able way  in  which  the  great  majority  of  cases  operated 
on  become  fat  and  flourishing  after  gastrojejunostomy 
for  non-mahgnant  affections,  the  improved  condition 
being  maintained  for  many  years.  There  is  at  least 
one  patient  who  at  the  age  of  seven  was  described 
by  his  father  as  strong  and  healthy,  with  good  appe- 
tite and  exceedingly  good  digestion,  after  a  gastro- 
jejunostomy at  the  age  of  eight  weeks  for  pyloric 
stenosis.  Paterson  has  proved  that  the  amount  of 
fat  and  protein  passed  in  the  faeces  without  assimila- 


*  Deut.  Zeit.  Chirurg.,  iqh. 


STOMACH     AND    INTESTINES  131 

tion  is  very  little  greater  than  in  the  normal  individual. 
In  four  cases  it  was  only  about  2  per  cent  above 
normal  ;  that  is,  the  faeces  contained  about  9  to 
9'5  per  cent  of  protein  nitrogen  taken  as  food 
instead  of  the  normal  77  per  cent.  Much  less 
favourable  results  previously  pubhshed  by  Joslin 
were  due  to  the  fact  that  he  used  cancerous  cases  on 
which  to  experiment.  Paterson's  results  are  confirmed 
by  Cameron,*  who  finds  that  the  only  ill-effect  is  some 
slight  diminution  in  the  power  of  absorbing  fat. 

ABSORPTION     IN     THE     COLON. 

We  may  sum  up  the  ordinary  functions  of  the 
various  parts  of  the  bowel  with  regard  to  absorption 
thus  : — 

Drugs,  salts,  and  sugars  are  absorbed  in  the 
stomach. 

Proteins  (as  aminoacids) ,  carbohydrates  (as  sugar), 
and  fats  (as  soap  and  glycerin)  are  absorbed  in  the 
small  intestine. 

Water  is  absorbed  in  the  large  intestine. 

The  practical  physician  or  surgeon  is  concerned 
with  the  physiologist's  answer  to  two  questions. 
First,  Is  the  colon  a  necessary  organ,  or  may  it  be 
ehminated  with  safety  ?  Second,  Can  the  large 
intestine  absorb  useful  foodstuffs  in  case  of  need  ? 

With  regard  to  the  first  point,  we  are  at  once  con- 
fronted with  the  fact  that  in  some  bats  the  colon  is 
exceedingly  short.  Again,  it  is  well  known  that 
patients  with  an  artificial  anus  in  the  caecum  are  able 

*  Brit.  Med.  Jour.,  1908,  i,  p.  140. 


132  FUXCTIOXS     OF    THE 

to  keep  up  their  nutrition.  The  same  is  true  after 
the  ileum  has  been  cut  across  and  turned  into  the 
sigmoid.  Careful  analyses  made  by  Groves  and 
Walker  Hall  under  these  conditions  show  that  the 
normal  amount  of  water  can  still  be  absorbed  by  the 
short  piece  of  rectum  and  sigmoid  traversed  by  the 
food  ;  the  faeces  are  not  too  fluid.  By  comparing  the 
amount  of  water  in  the  intestinal  contents  at  the 
ileocsecal  valve  and  as  passed  naturally  in  man, 
they  conclude  that  the  colon  absorbs  about  lo  to 
20  per  cent  of  water  from  the  faeces.  Bacteria 
make  up  nearly  half  the  weight  of  the  faeces  as 
passed  normally.  Treves,  Lane,  and  others  have 
excised  almost  the  whole  colon  without  the  patient's 
nutrition  suffering. 

We  conclude  then  that  the  colon  is  not  a  necessary 
organ.  If,  however,  a  permanent  artificial  anus  is 
made  in  the  ileum  more  than  12  to  18  inci'ies  away 
from  the  ileocaecal  valve,  absorption  is  inadequate, 
and  the  patient  dies  of  starvation. 

Turning  to  the  second  question,  it  is  scarcely 
necessary  to  call  attention  to  its  very  great 
importance.  If  the  colon  cannot  absorb  a  reasonable 
quantity  of  foodstuffs,  the  whole  theory  of  feeding 
by  nutrient  enemata  would  coUapse. 

In  the  experiments  described  above,  Groves  and 
Walker  Hall  found  that  the  absorption  of  nitrogen 
and  fat  by  the  colon  was  so  small  as  to  be  neghgible. 
Laidlaw  and  Ryffel,  analyzing  the  urine  during  rectal 
feeding,  found  that  the  nitrogen  output  corresponded 
pretty  closely  to  the  pubhshed  figures  for  pro- 
fessional fasting  men  at  the  same  date  of  starvation  ; 


STOMACH    AND     INTESTINES  133 

the  enemata  used  were,  however,  not  particularly 
suitable,  consisting  of  the  whites  of  nine  eggs,  six 
ounces  of  raw  starch,  and  twenty-four  ounces  of 
peptonized  milk.  The  albumin  and  starch  were 
probably  not  touched.  Langdon  Brown  found  no 
difference  in  the  urea  of  the  urine,  whether  the 
patients  were  given  peptonized  milk  or  normal  saUne. 
Careful  analysis  of  the  figures  given  by  Boyd  and 
Robertson,  and  also  a  number  of  observations  made 
by  the  present  writer,  furnish  convincing  evidence 
that,  as  measured  by  the  standard  of  the  nitrogen 
output  in  the  urine,  the  absorption  of  nitrogenous 
foodstuffs  from  the  rectum  is  practically  nil. 

Sharkey  and  others  claim  that  a  good  deal  of 
nitrogen  can  be  absorbed  by  the  rectum,  basing  their 
findings  on  the  analysis  of  rectal  washings  ;  but  this 
method  is  open  to  criticism,  as  sometimes,  in  spite  of 
washing  out,  the  patient  may  pass  an  enormous 
putrid  evacuation,  showing  that  lavage  was  not 
effectual. 

Now  this  failure  to  absorb  might  be  due  to  one 
of  two  causes.  First,  it  may  be  that  the  large 
intestine  has  no  power  of  absorbing  nitrogenous 
foodstuffs  in  any  form.  Second,  it  may  be  that  no 
erepsin  is  present  in  its  secretion,  so  that  there  are 
no  aminoacids  formed  from  the  peptone  of  the 
enema.  The  crucial  experiment  is.  Can  aminoacids 
be  absorbed  ? 

To  determine  this  the  writer,  with  Dr.  Bywaters, 
has  made  by  the  Kjeldahl  method  daily  analyses  of 
nitrogen  in  the  urine  in  patients  to  whom  enemata 
were  given,  either  of  milk  pancreatized  for  twenty- 


134  FUNCTIONS    OF    THE 

four  hours  so  as  to  convert  most  of  the  protein  into 
aminoacids,  or,  in  other  cases,  of  synthetic  amino- 
acids  (Merck).  Usually  ordinary  ward  nutrients, 
peptonized  for  twenty  minutes,  were  given  for  a 
few  days  first,  and  then  the  aminoacid  preparations 
used  instead.  In  each  of  five  patients  the  nitrogen 
output  in  the  urine  was  greatty  increased  by  the 
use  of  aminoacids  in  the  nutrients.  Figures  of  two 
such  cases  are  given  in  the  Appendix. 

We  conclude,  therefore,  that  aminoacids  can  be 
absorbed,  and  that  we  may  hope  to  give  nourishment 
to  patients  by  rectal  injections  of  milk  pancreatized 
for  twenty-four  hours,  although  ordinary  peptonized 
milk  is  a  failure. 

It  is  quite  certain  that  dextrose  can  be  absorbed 
from  the  rectum,  because  it  wiU  cure  acidosis  when 
given  in  this  way,  and  also  it  will  raise  the  respiratory 
quotient  by  increasing  the  amount  of  C0„  expired. 
Boyd  and  Robertson  showed  that  practically  no 
sugar  can  be  recovered  from  the  rectal  washings  of 
a  patient  given  peptone  and  sugar  enemata,  although 
peptone  is  always  returned.  Lactose  appears  not 
to  be  absorbed  ;   it  fails  to  control  acidosis. 

It  is  very  difficult  to  obtain  evidence  as  to  whether 
fats  are  absorbed.  In  a  patient  who  had  a  fistula 
of  the  thoracic  duct,  only  from  37  to  5*5  per  cent 
of  the  fat  given  per  rectum  was  recovered  from  the 
fistula. 

In  another  patient  the  thoracic  duct  was  blocked 
and  a  l^miphatic  vessel  had  ruptured  into  the  urinary 
passages,  so  that  most  of  the  fat  absorbed  by  the 
lacteals  escaped  into  the  urine,  which  became  milky 


STOMACH    AND    INTESTINES  135 

after  a  fatty  meal  (chyluria).  There  was  no  chyluria 
when  all  fats  were  stopped  by  mouth  and  nutrient 
enemata  containing  milk  administered. 

It  must  not  be  supposed  that  rectal  feeding 
supplies  absolute  rest  to  the  stomach.  It  may  be 
observed  in  patients  with  a  gastrostomy  wound  that 
each  nutrient  enema  excites  a  reflex  flow  of  gastric 

juice. 

Those  who  believe  in  the  possibility  of  feeding 
patients  satisfactorily  by  nutrient  enemata  usually 
rely  upon  some  incorrect  pubUshed  analyses  by 
Ewald,  an  observation  by  Leube  that  a  dog  can  be 
kept  aUve  for  many  months  by  injections  of  chopped 
meat  and  pancreas  (this  method  causes  toxic  sym- 
ptoms in  man),  and  the  remarkable  fact  that  the 
weight  may  be  fairly  well  sustained  at  first.  This 
happens  even  if  nothing  but  water  is  given,  and  is 
due  to  the  fact  that  the  patients,  usually  sufferers 
from  hcematemesis,  are  exsanguinated  to  start  with 
and  greedily  absorb  water.  Patients  have  been 
kept  alive  on  nutrients  for  several  weeks,  but  it 
is  well  known  that  there  are  sometimes  sudden  and 
unaccountable  deaths.  It  must  not  be  forgotten 
that  if  water  is  suppHed  Hfe  will  usually  be  prolonged 
for  a  month  with  no  food  at  all,  and  in  one  instance 
a  man  was  alive  after  sixty-four  days  of  complete 
starvation.  If  water  also  is  withheld,  death  takes 
place  in  about  a  week  ;  but  a  girl  buried  in  an  Italian 
earthquake  lived  eleven  days  without  either  food 
or  drink. 

We  conclude,  therefore,  that  feeding  with  nutrients 
composed  of  peptonized  milk  is   sheer  starvation, 


136  STOMACH    AND    INTESTINES 

but  that  better  results  may  be  obtained  with 
enemata  composed  of  dextrose  and  long-pancreatized 
milk. 

REFERENCES. 

FiSHBACK,  etc. — Amer.  Jour,  of  Physiol.,  1919,  xlix,  p.  174. 

Whipple,  etc. — Joiir.  Exper.  Med.,  19 16,  xxiii,  p.  123. 

Dragstedt,  etc. — Amer.  Jour,  of  Physiol.,  xlvi,  1918,  p.  366. 

DuNDON. — Ibid.,   191 7.  >^liv,  p.  234. 

Carlson.— Z&ff^.,  xlv,  p.  Si. 

Hurst. — The    Sensibility'  of  the  Alimentary  Canal.     Oxford 

Med.   Public,  191 1. 
SoLTAU  Fenwick. — Proc.  Royal  Soc.  Med.,  Surgical  Section, 

1910,  p.  177. 
Paterson. — Ibid.,  p.  187. 
Walton. — Lancet,  190S,  ii,  pp.  17,  85 
Groves. — Proc.   Royal    Soc.    Med.,    vol.    ii,    1909,    part    iii 

Surgical  Section,  p.  121. 
Langdon    Brown. — Proc.     Royal    Soc.    Aled.,    Therapeutic 

Section,  191 1,  p.  63. 
Hurst. — Jour,  of  Physiol.,  1913,  vol.  xlvii,  pp.  54,  57 
Sherren. — Brit.  Jour,  of  Surg.,  19 14.  Jan.,  p.  390. 
Rendle  Short  and  Bywaters. — Brit.  Med.  Jour.,  1913.  i> 

p.  1361. 
Carlson. — Amer.  Jour,  of  Physiol.,  1913,  p.  8. 


i;:57 


CHAPTER     VI. 
THE     GENITAL     GLANDS. 

FUNCTIONS      OF    THE      OVARY FUNCTIONS    OF      THE    TESTIS 

CONTROL      OF      THE       GENITAL       GLANDS       BY      INTERNAL 

SECRETIONS THE     SECRETION       OF    MILK THE      OVUM — 

CHEMICAL    DIAGNOSIS    OF    PREGNANCY. 

STUDENTS  of  physiology  do  not  usually  devote 
as  much  attention  to  the  functions  of  the 
reproductive  apparatus  as  the  clinical  importance  of 
the  subject  demands,  and  writers  of  text-books  have 
been  in  the  habit  of  relegating  it  to  a  very  brief 
chapter  at  the  end  of  the  book. 

FUNCTIONS     OF     THE     OVARY. 

The  functions  of  the  ovary  may  be  classed  under 
three  headings  :  the  production  of  ova,  the  control 
of  menstruation,  and  the  internal  secretion.  The 
corpus  luteum  has  other  functions,  to  be  considered 
separately. 

The  ovary  shows  on  microscopical  examination 
ripe  and  unripe  ova,  the  former  enclosed  in  the 
Graafian  folHcles,  corpora  lutea  of  varying  age,  and 
certain  glandular  interstitial  cells  which  probably 
furnish  the  internal  secretions,  and  are  supposed  to 
be  the  starting-point  of  multilocular  cystic  disease  of 
the  ovary.     We  shall  consider  menstruation  first. 

Menstruation. — We  shall  not  discuss  the  histology 
of  this  process,  except  to  say  that  the  mucous  mem- 


138  THE    GENITAL    GLANDS 

brane  of  the  uterus  becomes  greatly  thickened  and 
engorged  every  month,  and  haemorrhages  take  place 
into  it  which  carry  away  parts  of  the  superficial 
layers.  We  are  as  far  as  ever  from  understanding 
the  real  value  of  its  occurrence.  According  to  Blair 
Bell,  a  large  quantity  of  calcium  salts  accumulate 
in  the  blood,  which  menstruation  removes,  menstrual 
blood  being  very  rich  in  calcium. 

There  is  no  doubt  that  menstruation  is  determined 
by  an  internal  secretion  from  the  ovaries,  and  when 
these  are  both  removed  it  almost  invariably  ceases. 

Marshall  and  Heape  have  shown  that  the  process 
is  by  no  means  peculiar  to  the  human  subject.  In 
a  great  variety  of  animals,  such  as  deer,  dogs,  sheep, 
and  monkeys,  there  is  a  regular  cycle  of  changes 
leading  up  to  the  cestnim  or  rut,  and  after  great 
overgrowth  of  the  mucous  membrane  of  the  uterus 
there  is  a  mucous  and  often  bloodstained  discharge, 
followed  by  a  brief  period  of  fertility. 

Ovulation. — The  rupture  of  the  Graafian  follicle 
and  shedding  out  of  the  ovum  is  called  ovulation. 
It  has  been  much  debated  whether  the  time  of 
ovulation  coincides  with  that  of  menstruation  in  the 
human  subject.  In  the  animals  above  described  no 
doubt  this  is  true,  and  in  the  human  subject  the 
age-hmits  of  fertihty  and  of  menstruation  are 
approximately  the  same.  Nevertheless  the  relation- 
ship cannot  be  exact,  because  pregnancy  has 
occurred  before  the  first  menstruation,  and  observa- 
tions on  the  ovaries  during  abdominal  operations 
at  various  times   in  the  menstrual  cycle  show  that 


THE    GENITAL    GLANDS  139 

although  ovulation  commonly  takes  place  at  about 
the  same  time  as  menstruation,  this  is  by  no  means 
invariable.  If  it  were  so,  the  Jewish  race  would 
probably  have  become  extinct,  because,  in  obedience 
to  the  Levitical  law,  amongst  strict  Jews  husband 
and  wife  hve  apart  during  and  for  some  days  after 
menstruation. 

There   is   some   evidence   that   in   primitive   man 

there  was  only  one  annual  period  of  special  fertihty. 

There  is  a  Javan  tribe  amongst  which  all  the  births 

are  said  to  take  place  in  February.     Many  animals 

that  in  the  wild  state  only  go  into  oestrum  once  or 

twice  a  year  become  fertile  all  the  time  in  captivity. 

After  bilateral  removal  of  the  ovaries  the  patient 

is  of  course  sterile  and  menstruation  ceases,  but  in 

a   few   rare   cases,   apparently   owing   to    abnormal 

outlying    fragments    of    ovary    remaining    behind, 

pregnancy  has  occurred  and  menstruation  continued. 

By  some  mysterious  chemical  attraction,  the  shed 

ovum  finds  its  way  into  the  Fallopian  tube.     If  one 

tube  is  blocked,  the  other  may  receive  the  ovum, 

because  cases  are  not  very  infrequent   of  a  tubal 

pregnancy  on  one  side  with  the  corpus  luteum  in  the 

opposite  ovary. 

There  appears  to  be  in  some  famihes  a  hereditary 
tendency  at  each  ovulation  to  rupture  several 
Graafian  foUicles  and  shed  out  more  than  one  ovum 
at  a  time.  A  case  was  recently  reported  of  a  woman, 
age  35,  who  had  two  sets  of  quadruplets,  three  sets 
of  triplets,  and  five  sets  of  twins.  Her  mother  had 
twenty-eight  children,  and  her  grandmother  twenty- 
nine,  including  quadruplets  and  triplets.     In  another 


140  THE    GENITAL    GLANDS 

case  a  woman  had  four  twin  pregnancies,  her  mother 
and  aunt  one  each,  and  her  grandmother  two. 

Internal  Secretions  of  the  Ovary. — One  internal 
secretion  controls  menstruation.  Another,  or  the 
same,  appears  to  act  upon  the  vasomotor  system  ; 
when  it  is  withdrawn  by  artificial  removal  of  the 
ovaries  or  by  the  cessation  of  their  function  at  the 
menopause,  the  patient  often  suffers  from  flushings, 
headaches,  and  other  neuroses. 

Under  these  same  circumstances  the  breasts, 
uterus,  and  vagina  atrophy,  and  obesity  may  develop. 
The  influence  over  breast  tissue  extends  even  to 
cancerous  tumours  growing  in  it  ;  double  oophor- 
ectomy in  a  considerable  number  of  cases  of  inoperable 
cancer  has  caused  retrogression  of  the  growth,  and 
once  or  twice,  apparently,  a  cure  has  resulted.  On 
the  other  hand,  pregnancy  shortly  after  removal  of 
cancerous  breast  usually  leads  to  recurrence,  and 
during  pregnancy  a  cancer  of  the  breast  grows  with 
frightful  rapidity. 

We  do  not  possess  much  information  as  to  the 
consequences  of  removal  of  both  ovaries  in  little 
girls.  A  statement  appears  in  some  books  that  the 
operation  is  performed  in  Persia,  and  that  women  of 
a  masculine  type  result,  but  this  is  a  traveller's  tale. 

The  symptoms  of  the  artificial  menopause  following 
double  oophorectomy  may  be  much  relieved  by 
grafting  a  piece  either  of  the  patient's  ovary,  or  less 
satisfactorily  that  from  another  person,  into  the 
abdominal  wall.  In  some  cases  menstruation  has 
remained  unaffected,  and  when  the  graft  has  been 


THE    GENITAL    GLANDS  141 

into  the  peritoneum,  it  is  said  that  pregnancy  has 
occurred.* 

The  Corpus  Luteum.  —  After  ovulation  has 
occurred,  the  Graafian  follicle  becomes  converted 
into  a  gland  containing  a  yellow  fatty  pigment,  the 
corpus  luteum.  Ordinarily  this  is  quite  small  ;  if 
pregnancy  follows  it  may  reach  a  diameter  of  half  to 
three-quarters  of  an  inch.  Apparently  the  internal 
secretion  of  this  body  determines  the  fixation  of  the 
ovum  in  the  uterus,  and  perhaps  also  the  subsequent 
overgrowth  of  that  organ.  If  both  ovaries  are 
removed  early  in  pregnancy,  abortion  always  follows. 
In  extra-uterine  pregnancy  the  uterus  enlarges 
although  the  foetus  is  not  inside  it.  Removal  of  both 
ovaries  in  animals  or  in  the  human  subject  in  the 
later  months  of  pregnancy  does  not  usually  lead  to 
abortion  ;  one  patient  went  on  to  full  term  in  spite 
of  double  oophorectomy  as  early  as  the  sixth  week. 

Whether  the  internal  secretions  of  the  ovary  are 
due  to  the  corpus  luteum  or  to  the  interstitial 
glandular  cells  is  quite  uncertain.  There  is  some 
evidence  of  other  obscure  internal  secretory  functions 
besides  those  mentioned.  A  rare  disease  called 
osteomalacia,  characterized  by  softening  and  bend- 
ing due  to  decalcification  of  the  bones,  makes  great 
progress  during  pregnancy,  and  in  some  cases  at 
least  is  cured  by  a  double  oophorectomy. 

Ovarian  feeding  has  been  tried  to  reheve  the 
symptoms  of  the  natural  or  artificial  menopause,  but 
the   results   are   dubious.     It   is   always  difficult   to 

*  See  Archtv.  gen.  chirurg.,  1911,  p.  550. 


142  THE    GEXITAL    GLANDS 

foretell  when  an  internal  secretion  will  be  capable  of 
absorption  through  the  intestinal  wall  unchanged. 
Calcium  salts  have  been  used  for  the  same  troubles, 
and  in  some  cases,  at  least,  work  remarkably  well. 

FUNCTIONS     OF     THE     TESTIS. 

The  most  obvious  function  of  the  testis,  of  course, 
is  to  produce  spermatozoa,  which  it  continues  to  do 
well  on  into  old  age. 

The  testis,  however,  contains  other  secretory  cells 
between  the  tubules,  sometimes  called  the  cells  of 
Leydig,  and  to  these  is  attributed  the  production  of 
an  internal  secretion.  It  is  not  uncommon  for  one 
or  both  testes  to  fail  to  descend  (cryptorchism),  and 
in  bilateral  cases  the  individual  is  nearly  always 
sterile,  but  the  secondary  sexual  characters  are 
usually  preserved.  On  microscopical  examination 
the  tubules  are  Httle  developed,  but  the  interstitial 
cells  of  Leydig  appear  to  be  normal. 

It  has  been  much  debated  whether  the  failure  to 
descend  is  the  cause  or  the  consequence  of  the  failure 
to  develop,  and  on  the  answer  to  this  question 
depends  the  surgical  treatment  ;  if  the  first  is  true, 
it  is  highly  desirable  to  find  some  operative  procedure 
which  will  ensure  the  testis  a  permanent  resting- 
place  in  the  scrotum,  but  the  evidence  goes  to  show- 
that  this  does  not  lead  to  proper  growth  of  the  gland, 
so  we  must  conclude  that  descent  fails  because  it  is 
not  worth  while  for  the  gubernaculum  to  bring 
down  a  defective  organ. 

When  the  testes  on  both  sides  are  removed  after 
puberty,  the  consequences  are  sterihty,  atrophy  of 


THE    GENITAL    GLANDS  14;} 

the  prostate  gland,  and  in  a  few  cases  in  old  men 
mental  impairment.  The  secondary  sexual  characters 
are  not  lost,  and  it  is  very  doubtful  if  the  dotage 
which  has  sometimes  followed  is  really  due  to  loss  of 
any  internal  secretion  or  nervous  influence  ;  most 
probably  it  is  merely  the  consequence  of  a  mutilating 
operation  preying  on  the  mind  of  a  broken-down 
indi\idual.  In  younger  and  healthier  adults  there 
is  no  mental  change  or  loss  of  capacit}'. 

The  atrophy  of  the  prostate  is  not  constant,  but 
the  effects  of  castration  have  been  taken  advantage 
of  to  reduce  the  size  of  a  prostatic  enlargement 
causing  obstruction.  Ligature  or  excision  of  the  vas 
deferens  blocks  the  way  for  the  external  secretion 
of  the  testis,  and  leads  to  atrophy  of  the  tubules 
and  consequent  steriUty,  but  the  internal  secretion 
of  the  interstitial  cells  is  not  affected  unless  the 
main  vessels  of  the  cord  are  tied. 

In  boys,  the  results  of  castration  are  more  far- 
reaching,  causing  not  only  sterihty  but  also  failure  of 
the  secondar}^  sexual  characters  (eunuchism).  As 
is  well  known,  the  operation  has  been  practised  for 
centuries  upon  the  attendants  and  guards  of  the 
harem  at  Oriental  courts.  The  beard  and  moustache 
do  not  usually  appear,  the  voice  is  childish,  the  body 
fat,  and  the  mental  attitude  to  the  world  modified, 
although  there  is  no  loss  of  business  capacity.  The 
prostate  and  vesiculae  are  atrophic,  but  there  is  not 
necessarily  impotence.  In  cocks,  testicular  grafting 
partially  obviated  the  effects  of  castration.  Indeed, 
it  is  even  recorded  that  in  a  hen,  after  removal  of  the 
ovaries,  testicular  grafting  caused  the  bird  to  grow 


144  THE    GENITAL    GLANDS 

a  comb,  wattles,  and  spurs,  and  start  to  crow,  but 
this  requires  confirmation. 

Following  upon  Brown-Sequard's  famous  con- 
tention that  feeding  or  injection  of  testicular  extract 
had  made  him  at  72  a  young  man  again,  attempts 
have  been  made,  especially  by  vendors  of  expensive 
patent  remedies,  to  convince  the  profession  that  the 
internal  secretion  of  the  testis  can  be  taken  as  a 
rejuvenating  drug,  recalling  the  classical  story  of 
Medea's  cauldron;  but,  as  Biedl  says,  "exact  and 
carefully  controlled  experiments  with  this  substance 
have  not  been  described  ".  Auto-suggestion  probably 
accounts  for  much  of  the  alleged  benefit. 

CONTROL  OF  THE  GENITAL  GLANDS  BY 
INTERNAL  SECRETIONS. 

Not  only  are  the  genital  glands  themselves  the 
source  of  internal  secretions,  but  there  is  a  good 
deal  of  accumulating  though  ill-assorted  evidence  to 
show  that  their  own  activity  is  dependent  upon 
chemical  messengers  (hormones),  reaching  them  by 
the  blood-stream,  derived  from  what  we  call  the 
ductless  glands. 

What  is  it  that  makes  a  man  mascuHne  and  a 
woman  feminine  ?  It  used  to  be  thought  that  the 
testis  and  the  ovary  were  solely  responsible.  Now 
we  know  that  masculinity  and  femininity  may 
persist  even  after  these  glands  are  rem^oved.  The 
mere  fact  of  infertihty  does  not  abolish  sex,  which  is 
dependent  upon  the  combined  working  of  a  num- 
ber of  internal  secretions. 


THE    GENITAL    GLANDS  145 

The  Ductless  Glands  before  Puberty.  —  In 
young  animals  and  in  children  the  development  of 
the  ovary,  testis,  and  other  parts  of  the  genital 
apparatus  depends  upon  chemical  stimuli  received 
from  the  pituitary  and  thyroid  glands.  Experimental 
removal  of  these  glands  in  young  animals,  or 
insufficiency  diseases  of  either  of  them  in  man, 
may  lead  to  sexual  infantihsm. 

On  the  other  hand,  great  enlargement,  and  therefore 
presumably  hypersecretion,  of  the  cortex  of  the 
suprarenal  (hypernephroma)  causes  precocious  sexual 
development  of  the  male  type.  In  boys  this  leads  to 
overgrowth  of  the  sexual  organs,  with  early  activity. 
In  girls,  there  is  enlargement  of  the  clitoris,  growth 
of  hair  on  the  face  and  pubes,  and  sometimes  a  male 
type  of  external  genitals  (pseudo-hermaphroditism), 
but  there  is  not  premature  menstruation  or 
fertility. 

Very  few  cases  of  overgrowth  of  the  pineal  gland 
are  on  record,  but  in  some  of  these  there  has  been 
sexual  precocity  in  boys. 

Sexual  precocity  in  girls  is  not  uncommon  ;  it 
appears  to  be  due  to  excessive  ovarian  secretion. 
In  one  case  a  girl  seven  years  old  showed  precocious 
development  and  menstruation  ;  an  ovarian  swelhng 
was  removed,  and  the  signs  of  puberty  subsided. 

It  is  found  in  gynaecological  practice  that  thyroid 
and  pituitary  feeding  may  hasten  puberty  in  cases 
where  it  is  unduly  delayed.  After  twenty,  how- 
ever, a  small  uterus  cannot  be  stimulated  to  grow. 

We  have  no  sufficient  evidence  yet  of  the  value  or 
otherwise  of  feeding  with  the  ductless  glands  in  cases 
of  cryptorchism  with  atrophic  testes. 

10 


146  THE     GENITAL     GLANDS 

The  Ductless  Glands  after  Puberty, — Here 
again  deficient  internal  secretion  of  the  thyroid 
gland  appears  to  be  a  cause  of  amenorrhoea,  painful 
menstruation,  and  monthl}^  pain  in  the  breasts,  and 
Blair  Bell  states  that  thyroid  feeding  cures  many 
such  cases.  It  is  of  course  well  known  that  myx- 
oedema  leads  to  amenorrhoea  and  sterility. 

In  cases  of  pituitary  disorder,  also,  amenorrhoea 
and  sterility  are  the  rule  in  women,  and  impotence 
in  men.  These  are  probably  due  to  deficiency  of 
the  pituitary  secretion,  but  this  is  not  very  clear. 

Not  only  do  the  secretions  of  the  ductless  glands 
influence  the  genital  organs,  but  there  is  evidence  of 
an  effect  in  the  reverse  direction.  During  pregnane}' 
the  thyroid  gland  usually  enlarges  a  little  ;  in  Italy 
this  has  been  taken  for  years  as  a  sign  of  conception. 
The  pituitary  gland  also  shows  enlargement  (Erdheim 
and  Stumme).  Berry  points  out  that  adenomatous 
goitre  nearly  always  occurs  in  single  or  nulhparous 
women. 

It  has  already  been  stated  that  removal  of  the 
ovaries  is  a  remedy  for  osteomalacia  ;  Bossi  has 
recently  advanced  evidence  that  the  same  effect  may 
be  produced  more  conveniently  by  injections  of 
adrenalin. 

THE     SECRETION     OF     MILK. 

It  is  a  very  striking  phenomenon  that  after  twenty 
or  thirty  years  of  quiescence  the  mammary  glands 
should  suddenly  spring  into  activity  on  the  very  day 
when  the  secretion  is  required.  It  cannot  be  due  to 
nervous    influences,    because    there    is    no    nervous 


THE    GENITAL    GLANDS  147 

mechanism  controlling  the  flow  of  milk.  For  this 
reason  pilocarpine  does  not  increase  and  belladonna 
preparations  do  not  check  the  secretion,  in  spite  of 
their  ancient  reputation  founded  on  analogy.  It  is 
true  that  when  the  child  is  put  to  one  breast  the 
other  may  pour  out  a  little  milk,  but  this  is  due  to 
reflex  contraction  of  the  muscle  about  the  ampullae 
of  the  ducts.  The  only  drug  which  increases  the 
flow  of  milk  is  pituitary  extract,  but  here  again  the 
action  is  probably  on  the  muscle,  not  on  the  gland 
cells. 

The  physiological  stimulus  which  starts  the 
lactation  is  an  internal  secretion  derived  from  the 
foetus.  Injection  of  extracts  of  foetal  animals  into 
a  non-pregnant  female  of  the  same  species  brings 
about  hypertrophy  and  functional  activity  of  the 
mammary  glands  (StarUng  and  Lane-Claypon) .  The 
statement  that  this  hormone  is  derived  from  the 
ovary  can  scarcely  be  true,  because  lactation  is 
normal  after  double  oophorectomy.  It  is  not  un- 
common for  the  rudimentary  breasts,  even  of  the 
foetus,  to  be  stimulated  to  a  few  days'  activity 
('  witch's  milk ').  One  of  a  pair  of  conjoined 
Siamese  twins  was  recently  deUvered  of  a  child, 
and  both  commenced  lactating. 

Once  started,  the  secretion  of  milk  is  kept  up  by 
suction.  When  this  ceases,  the  glands  return  to  the 
quiescent  state. 

THE     OVUM. 

The  epithehal  and  other  cells  of  the  adult  are  not 
immortal,   and  require   frequent   renewal   to   repair 


148  THE    GENITAL    GLANDS 

daily  wear  and  tear.  The  cell-divisions  bringing 
this  about  are  initiated  by  the  division  of  a  body 
outside  the  nucleus,  called  the  centrosome,  which 
forms  the  achromatic  spindle.  A  skein  appears  in 
the  nucleus,  which  divides  into  V-shaped  bodies 
called  chromosomes,  which  in  man  are  twenty-four 
in  number.  Each  chromosome  sphts  into  two,  form- 
ing forty-eight  ;  of  these,  twenty-four  pass  to  one 
daughter  nucleus  and  twenty-four  to  the  other. 
Finally,  the  cell  protoplasm  cleaves,  and  the  nucleus 
returns  to  its  resting  condition.  This  process  is 
called  homotype  (i.e.  normal)  mitosis. 

Before  it  meets  a  spermatozoon,  the  nucleus  of 
the  ovum  divides  twice,  extruding  the  two  polar 
bodies.  At  the  second  of  these  divisions,*  half  the 
chromosomes — that  is,  in  man,  twelve — are  thrown 
out,  and  the  centrosome  with  them.  This  is  to 
prevent  parthenogenesis  —  the  development  of  an 
o\n.im  into  a  foetus  without  a  male  element.  In 
bees  and  wasps,  where  parthenogenesis  occurs,  tliis 
second  or  hcterotype  mitosis  does  not  take  place. 

In  the  formation  of  the  spermatozoon,  also,  a 
cell  with  twenty-four  chromosomes  divides  into  two 
spermatozoa  with  twelve  each ;  the  head  is  the 
nucleus,  the  neck  the  centrosome,  and  the  tail  is  the 
cell  body.  Thus  the  foetus  starts  Hfe  with  twenty- 
four  chromosomes,  twelve  from  each  parent.  In 
these,  according  to  Weissmann,  is  bound  up  its 
heredity,  including  the  impulse  to  assume  the  general 
shape   of   mankind,    the   \dscera   with   their   proper 

•  Some  English  text-books  incorrectly  say  the  first. 


THE    GKNITAL    GLANDS  149 

anatomy  and  functions,  and  some  resemblance  to 
the  facial  appearance  and  even  the  tone  of  voice  and 
character  of  the  parents.  How  all  this  is  crowded 
into  such  microscopical  objects  is  the  greatest  marvel 
in  biology. 

The  spermatozoon  probably  brings  in  some 
chemical  factor,  at  any  rate  in  sea-urchins  and 
starfish,  because  in  these  animals  the  purely  female 
ovum  can  be  induced  to  develop  into  a  larva  by  con- 
centrated sea-water,  tannin,  or  even  violent  shaking. 
Perhaps  these  animals  arc  not  far  removed  from 
parthenogenesis,  and  the  part  played  by  the  male 
in  vertebrates  is  probably  more  important.  Recently, 
however,  it  has  been  stated  that  stabbing  an  un- 
fertilized frog's  ovum  will  make  it  develop  as  far  as 
the  tadpole  stage,  but  no  further. 

After  fertihzation,  the  ovum  starts  to  divide  into 
two,  four,  eight,  and  so  on.  Much  hght  is  thrown 
upon  the  process  by  the  phenomenon  of  identical 
twins.  Ordinary  twins,  due  to  the  fertihzation  of 
two  ova  by  two  spermatozoa,  are  no  more  alike  than 
any  other  pair  of  brothers  or  sisters.  Identical  twins 
probably  result  from  the  accidental  separation  of  the 
two  cells  produced  from  the  first  division  of  a  fertiliz- 
ation ovum,  and  the  children  have  an  identical 
heredity.  They  are  exactly  alike  in  sex,  appearance, 
and  even  in  deformities  such  as  hernia.  This  shows 
that  the  sex  and  general  conformation  of  the  child 
are  probably  fixed  from  the  moment  when  a  particular 
ovum  and  a  particular  spermatozoon  meet. 

The  causation  of  sex  is  still  a  puzzle.  It  has  been 
suggested  that  the  left  ovary  gives  rise  to  ova  that 


150  THE    GENITAL    GLANDS 

will  produce  girls,  and  the  right  ovary  generates 
boys,  so  that,  as  a  critic  remarked,  it  might  be  possible 
to  prevent  a  national  disappointment  by  removing 
a  queen's  left  ovar^^  Differences  in  feeding  a  set  of 
developing  embr^-os  are  said  to  alter  the  proportion 
of  males  and  females,  but  this  is  probably  due  to  an 
excess  in  mortality  of  the  one  or  the  other.  It  is  an 
ancient  tradition  that  during  a  great  war  more  boys 
than  girls  are  bom  because  the  m.others  are  physically 
superior  to  the  male  weaklings  who  have  not  gone 
to  the  front,  but  Europe's  recent  ordeal  lends  very 
little  support  to  the  theory.  Bearing  on  the  view 
that  the  offspring  is  likely  to  belong  to  the  same  sex 
as  the  feebler  parent,  it  may  be  mentioned  that 
statistics  have  been  published  sho\ving  that  when 
the  man  is  older  than  the  wife,  male  births  are  to 
female  as  113  to  100  (the  general  average  for  all 
births  is  106  boys  to  100  girls)  ;  when  the  parents' 
ages  are  the  same,  there  are  93-5  boys  to  100  girls  ; 
and  when  the  woman  is  older,  88-2  boys  to  100  girls. 
These  figures  are  corroborated  by  some,  but  contra- 
dicted by  others.  It  is  said  that  when  old  men 
marry  young  wives  (a  May  and  December  wedding) 
the  children  are  usually  boys.  A  German  writer, 
drawing  his  observations  from  the  relation  between 
the  time  of  a  soldier's  leave,  the  time  in  the  cycle  of 
the  wife's  menstrual  periods  when  he  was  at  home, 
and  the  sex  of  the  next  child,  concluded  that  concep- 
tion just  after  menstruation  leads  to  the  birth  of  boys, 
and  conception  later  to  the  birth  of  girls.  None 
of  these  theories  rests  on  any  sufficient  evidence. 
A  more  hopeful  explanation  may  be  based  on  the 


THE    GENITAL    GLANDS  151 

fact  that  in  some  invertebrates  there  is  an  additional 
X  chromosome  in  all  the  female  ova,  but  only  in 
half  the  male  spermatozoa  ;  fertilization  by  a 
spermatozoon  li'ith  the  x  chromosome  gives  rise  to 
females,  and  without  it  to  males.  If  this  is  true, 
sex  is  pure  chance,  unless  variations  in  the  health 
of  the  father  affect  the  proportion  of  the  two  types 
of  spermatozoa. 

CHEMICAL     DIAGNOSIS     OF     PREGNANCY. 

When  an  unusual  protein  passes  repeatedly  into 
the  circulation,  antibodies  of  a  ferment  nature  are 
produced  to  destroy  it.  Some  protein  from  the 
placenta  passes  into  the  maternal  blood-stream 
during  pregnancy.  Abderhalden  has  based  upon 
this  a  method  of  serum  diagnosis.  Fresh  placenta 
is  treated  with  the  patient's  serum,  and  if  she  is 
pregnant,  peptones  are  formed  by  digestion.  These 
can  be  dialysed  off  through  an  animal  membrane, 
and  tested  for  by  the  biuret  reaction.  Though 
requiring  extreme  care  in  the  technique,  the  method 
appears  to  be  sufficiently  accurate  and  reUable  to  be 
of  some  clinical  value. 

REFERENCES. 

Marshall. — The  Physiology  of  Reproduction. 
BiEDL. — The  Internal  Secretory  Organs,    19 13. 
Blair  Bell. — Proc.  Royal  Soc.  Metf. -(Obstetric  Section),  1913. 
Dec,   vol.  vii,  p,  47, 


152 


CHAPTER     VII 
THE     GROWTH     OF     BONE. 

RECENT  CHANGE  IN  OUR  CONCEPTION  OF  THE  GROWTH  OF 
BONE — OSTEOBLASTS— INCREASE  IN  THE  LENGTH  OF 
BONE— INCREASE   IN   THE   GIRTH    OF   BONE — FUNCTION   OF 

THE       PERIOSTEUM THE       REGENERATIVE       POWERS       OF 

BONE APPLICATION         OF        MODERN        RESEARCHES        TO 

SURGICAL  PRACTICE — BONE-GRAFTING RELATION  OF  THE 

DUCTLESS    GLANDS    TO    THE    GROWTH    OF    BONE. 

TWO  closely  allied  problems,  how  bones  increase  in 
length  and  girth  in  the  child,  and  how  regenera- 
tion of  new  bone  takes  place  after  loss  or  injury,  are 
of  great  interest  and  practical  importance  in  surgery. 
Every  case  of  separation  of  an  epiphysis  by  accident, 
and  every  operation  on  the  growing  end  of  a  bone 
in  children,  involves  a  consideration  of  the  first 
problem  ;  every  case  of  fracture,  necrosis,  periostitis, 
or  osteomyelitis  depends  for  its  proper  understand- 
ing and  rational  treatment  upon  the  second.  A  very 
important  research  has  recently  been  pubUshed  which 
necessitates  a  careful  reconsideration  of  some  of  our 
conceptions  of  this  subject. 

We  may  summarize  the  traditional  teaching  thus. 
Bone  is  laid  down  by  certain  cells  called  osteoblasts. 
In  young  animals,  these  are  the  direct  descendants 
of  cartilage  cells.  When  the  cartilage  becomes 
vascular,  the  cells  undergo  proliferation  for  a  time  ; 
when   they  assume  their  individual  maturity  they 


THE    GROWTH    OF    BONE  163 

cease  to  divide,  and  lay  down  calcareous  salts  all 
around  themselves  just  as  a  coral  polyp  does  ;  they 
are  included  in  the  midst  of  the  bone  thus  formed  as 
bone  corpuscles. 

Increase  in  the  le7tgth  of  the  bone  takes  place  by 
the  new  additions  at  each  end,  where  the  layer  of 
cartilage  between  the  shaft  and  the  epiphysis  is  con- 
stantly being  transformed  into  bone  ;  but  inasmuch 
as  its  cells  keep  on  dividing,  the  cartilage  is  not  used 
up  in  the  process  until  the  age  of  eighteen  to  twenty- 
five  is  reached.  It  is  usual  for  one  epiphysis  to  unite 
later  than  the  other,  and  in  that  case  the  increase  of 
length  is  greater  at  this  end  than  at  the  opposite,  and 
the  nutrient  artery  to  the  shaft  will  be  directed  away 
from  the  persistent  epiphysis  because  the  bone  is,  as 
it  were,  pushed  down  inside  the  periosteum. 

So  far,  the  results  of  recent  investigation  entirely 
support  and  ampHfy  the  older  opinion.  A  classical 
experiment  of  John  Hunter's  may  be  quoted.  He 
inserted  two  leaden  shot  into  the  tibia  of  a  young 
pig,  exactly  two  inches  apart.  When  the  animal  had 
grown  up,  he  found  that  although  the  bone  v/as  of 
course  much  longer,  the  shot  were  still  exactly  two 
inches  apart.  Evidently,  then,  the  increase  of  length 
must  have  been  at  the  ends,  not  by  interstitial 
increase  of  the  shaft. 

More  recently.  Mace  wen  has  removed  almost  the 
whole  shaft  of  the  right  radius  in  a  young  dog  by 
the  subperiosteal  method,  leaving  the  two  ends. 
After  six  weeks,  there  was  strong  and  vigorous  growth 
from  each  epiphysis,  and,  aided  by  a  bending  of  the 
ulna,  the  two  ends  had  come  together,  although  no 


154  THE    GROWTH    OF    BONE 

periosteal  growth  of  bone  had  taken  place.  One  of 
the  epiphyses  was  damaged ;  from  this  end  the  new 
bony  development  was  slenderer  than  from  the  un- 
injured end. 

In  another  experiment,  two  and  a  half  inches  of 
bone  with  its  periosteum  were  removed  from  the 
radius  of  a  young  dog,  and  metal  caps  fitted  over 
the  sawn  extremities  of  the  shaft  remaining  in  situ. 
Seven  weeks  later,  the  gap  was  found  completely 
bridged  by  bone,  and  the  two  metal  caps  had  come 
together.  Owing  to  bending  of  the  ulna,  they  did 
not  absolutely  meet,  but  passed  one  another  laterally. 

In  yet  another  case,  the  plate  of  cartilage  between 
the  shaft  and  epiphysis  was  removed  from  the  radius 
of  a  young  dog.  The  bone  failed  to  grow  at  that  end, 
and  a  lateral  expansion  of  the  epiphysis  became 
attached  to  the  ulna  and  stunted  its  growth  also. 
This  experiment  is  of  course  paralleled  in  man, 
when  a  separation  of  an  epiphysis  takes  place,  or 
when  the  growing  end  is  removed  in  the  excision  of 
a  joint. 

Increase  in  the  girth  of  bone  has  been  attributed  to 
the  periosteum.  Between  it  and  the  bone,  osteoblasts 
are  to  be  found  in  young  animals,  and  these  lay  down 
ring  after  ring  of  concentric  lamellae.  If  the  develop- 
ing animal  is  fed  with  pigment,  such  as  madder,  for  a 
short  period,  there  may  be  found  months  later  a 
buried  pigmented  ring  of  bone  which  was  laid  down 
at  that  time.  Another  classical  experiment  we  owe  to 
Duhamel  (1739),  who  buried  a  silver  ring  under  the 
periosteum  of  a  young  animal,  and  found  some  time 
after  that  the  ring  had  become  covered  by  subsequent 
bone  formation. 


THE     GROWTH     OF    BONE  155 

It  was  the  natural  corollary  from  this  belief,  that 
when  bone  has  been  destroyed  by  inflammation  or 
removed  by  operation,  we  must  look  to  the  periosteum 
to  regenerate  new  bone  ;  and  as  a  matter  of  fact  it  is 
well  known  that  if  the  periosteum  is  stripped  up  from 
the  shaft  by  a  purulent  collection  beneath  it,  it  does 
in  most  cases  lay  down  a  sheath  of  bone  outside  the 
space  in  which  the  pus  la}'.  Again,  after  fractures 
we  look  to  the  periosteum  to  produce  ensheathing 
callus  to  bind  the  broken  ends  together  again.  Some 
regenerating  power,  however,  must  be  allowed  to 
osteoblasts  derived  from  the  bone  itself,  to  explain 
the  formation  of  callus  between  the  actual  fractured 
ends  and  in  the  medullary  cavity. 

Well  entrenched  as  this  view  has  been,  it  has 
recently  been  subjected  to  most  damaging  criticism 
by  Sir  WiUiam  Macewen,  who  goes  so  far  as  to  state 
that  the  function  of  the  periosteum  is  not  to  produce 
bone  but  to  limit  the  production  of  bone,  and  that 
osseous  regeneration  takes  place  from  the  osteoblasts 
of  the  bone  itself,  not  from  the  periosteum.  He 
supports  his  thesis  by  some  most  interesting  experi- 
ments on  animals,  and  observ^ations  on  man. 

It  has  always  been  admitted  that  some  power  of 
laying  down  bone  must  be  allowed  to  osteoblasts 
quite  apart  from  the  epiphyseal  cartilages  or  the 
periosteum,  because  of  course  it  is  their  province  to 
fill  in  the  Haversian  canals  with  concentric  rings  of 
new  bone,  and  also  to  cement  the  ends  of  a  fracture 
as  intermediary  and  intramedullary  callus.  The  hard- 
ness and  density  of  bone  rather  blind  our  eyes  to  the 
fact  that,  like  every  other  living  tissue,  the  processes 


156  THE    GROWTH    OF    BONE 

of  building  up  and  breaking  down,  absorption  and 
new  formation,  are  continually  going  on  in  its  cells 
and  molecules.  When  it  is  irritated,  as  for  instance 
when  a  pin  is  driven  into  compact  bone,  absorption 
takes  place,  and  the  pin  may  loosen  in  the  course  of  a 
day  or  two  ;  when  it  is  withdrawn,  osteoblasts  wander 
into  the  track  and  fill  it  with  new  bone.  Even  so  soft 
an  organ  as  the  tongue  helps  to  maintain  the  shape  of 
the  jaw,  and  after  a  successful  operation  for  cancer 
the  lower  teeth  come  in  time  to  slope  towards  the 
buccal  cavity.  The  interstitial  changes  in  bone  are 
affected  by  various  toxins  and  internal  secretions  : 
during  rickets  the  osseous  tissue  is  at  first  softened, 
and  finally  becomes  more  compact;  the  pituitary 
secretion  causes  it  to  undergo  hypertrophy. 

So  much  is  known  and  admitted.  The  evidence 
which  enables  ^lacewen  to  go  further  and  to  deny 
any  share  to  the  periosteum,  as  such,  is  as  follows: — 

In  a  dog,  a  strip  of  periosteum  a  quarter  of  an 
inch  broad  and  two  inches  long  was  peeled  up  from 
the  radius,  leaving  the  attachment  to  the  epiphysis 
intact.     It  was  buried  between  muscles. 

Eight  weeks  later,  there  was  no  trace  of  bone 
formation  in  the  fibrous  intermuscular  band  which 
represented  the  periosteum.  On  the  other  hand, 
there  was  a  bony  ridge  outgrown  from  the  area 
whence  it  had  been  stripped  up.  So  far  then  from 
forming  bone,  the  periosteum  must  have  been  pre- 
venting the  outgrowth  of  bone. 

In  other  experiments,  a  strip  of  periosteum  was 
excised  and  immediately  implanted  in  the  neck  of  the 
same  animal  around  the  jugular  vein.     Usually  it 


TIIK    GROWTH    OP'    BONE  157 

was  entirely  absorbed  ;  once  a  tiny  osseous  nodule 
was  found,  derived  probably  from  an  attached  chip 
of  bone.  Macewen  points  out  the  great  practical 
importance  of  this  in  such  an  operation  as  sub- 
periosteal excision  of  the  elbow.  If  care  is  not  taken 
to  inspect  the  periosteum,  adherent  bony  flakes  may 
be  left  which  will  grow,  and  lock  the  joint.  If  they 
are  all  removed,  an  excellent  free  joint  results.  This 
represents  the  experience  of  over  two  hundred 
cases.  On  the  other  hand,  care  must  be  taken 
not  to  encroach  on  the  diaphysis  of  the  humerus  by 
removing  too  much,  or  it  may  sprout  new  bone. 

In  other  experiments,  Macewen  removed  portions 
or  the  whole  length  of  a  bone  subperiosteally.  No 
regeneration  took  place  to  fill  the  gap,  except  in  a 
few  cases  where  the  animal  was  young,  and  the  grow- 
ing epiphyseal  ends  pushed  the  extremities  together 
to  diminish  or  obhterate  the  gap.  No  new  periosteal 
bone  was  formed. 

He  then  repeated  Duhamel's  silver-ring  observa- 
tion, and  found  that  the  bur\ang  beneath  new  osseous 
tissue  occurred  just  as  well  if  the  bone  in  that  neigh- 
bourhood, or  indeed  in  its  whole  length,  was  first 
deprived  of  periosteum.  The  new  bone  could  be 
seen  overflowing  the  ring  from  the  edges.  In  this 
case  it  is  perfectly  evident  that  the  osteoblasts 
providing  for  growth  must  have  come  from  the  shaft, 
not  from  the  periosteum. 

A  number  of  important  observations  are  recorded 
demonstrating  the  regenerarive  powers  of  bone  itself, 
apart  from  periosteum,  and  more  particularly  m 
young  animals.     These  may  be  briefly  summarized. 


158  THE    GROWTH    OF    BONE 

Although  grafts  of  periosteum  into  the  neck  will  not 
grow  osseous  tissue,  thin  shavings  of  bone  itself, 
similarly  transplanted,  will  double  in  length  and 
thickness  in  most  cases.  In  a  number  of  experiments, 
pieces  of  bone  an  inch  or  more  in  length,  or  even 
comprising  the  whole  shaft  of  a  long  bone,  were 
successfully  transplanted  from  one  dog  to  another. 
In  a  classical  case,  Macewen  built  up  a  new  humerus 
for  a  lad  who  had  lost  the  shaft  by  acute  necrosis, 
and  although  the  wedges  of  bone,  derived  from 
excisions  for  deformed  legs,  were  not  covered  with 
periosteum,  they  grew  and  consolidated,  and  now, 
more  than  thirty  years  after,  aided  by  the  great 
growth  of  the  upper  epiphysis,  which  has  contributed 
the  bulk  of  the  humerus,  the  arm  is  strong  and 
useful.  In  other  cases,  fragments  of  bone  have  been 
replaced  to  fill  gaps  in  the  skull,  with  excellent 
results. 

Macewen  has  secured  osseous  growth  by  trans- 
plantation of  bone  chips  into  the  omentum,  and  also, 
after  burying  glass  tubes  in  the  middle  of  a  long 
bone,  he  has  found  the  lumen  of  the  tube  invaded  by 
osteoblasts,  and  osseous  islands  laid  down.  In  one 
interesting  case,  a  traumatic  aneurysm  formed  from 
the  brachial  artery  of  a  young  patient  in  consequence 
of  the  penetration  of  the  vessel  by  a  spicule  of  the 
humerus,  which  was  fractured.  Osteoblasts  washed 
out  of  the  humerus  were  thus  distributed  throughout 
the  clot  hning  the  aneurysm,  and  it  developed  a 
regular  bony  wall.  This  would  probably  occur  more 
frequently  when  the  aorta  erodes  the  vertebrae,  but 
for  the  fact  that  in  that  case  the  patient's  osteoblasts 
are  usually  senile. 


THE    GROWTH     OF    BONE  169 

In  some  experiments,  after  removing  a  length  of 
the  radius  with  its  periosteum,  the  gap  was  filled 
with  bone  chips.  Consolidation  took  place,  but  a 
large  tumour-like  mass  of  callus  formed,  infiltrating 
the  surrounding  muscles.  The  osteoblasts  from  each 
chip  had  wandered  out  and  prohferated,  and  when 
they  became  mature  had  surrounded  themselves 
with  calcareous  deposit,  which  bound  together  not 
only  the  detached  fragments  and  the  broken  ends, 
but  also  the  muscles  and  tendons  in  the  neighbour- 
hood. 

The  experimental  and  chnical  work  of  Hey  Groves 
on  fractures  strongly  supports  the  view  that  callus  is 
derived  from  bone  and  not  from  periosteum. 

The  factors  which  induce  bone-corpuscles  to 
become  active  and  prohferate  are  not  perfectly 
understood.  Macewen  lays  stress  on  rehef  from 
pressure,  and  no  doubt  this  has  great  importance. 
Dissemination  of  osteoblasts  by  increased  vascularity 
of  the  part  is  another  factor.  The  periosteum,  v/hen 
intact,  limits  the  osteoblasts  to  their  own  proper 
sphere,  and  prevents  their  encroaching  on  the 
muscles  and  fascial  planes. 

According  to  some  German  and  French  observa- 
tions, blood-clot  has  an  influence  not  only  in  pro- 
viding a  suitable  medium  in  which  bone  may  be 
formed,  but,  further,  in  exerting  a  direct  chemical 
stimulus  upon  the  osteoblasts. 

We  may  now  apply  these  researches  to  surgical 
practice,  considering  first  the  consequences  and 
repair  of  fractures.  In  subperiosteal  fractures,  rapid 
and  firm  union  takes  place  without  any  ensheathing 


160  THE    GROWTH    OF    BONE 

callus,  and  the  bone  feels  quite  normal  after  a  few 
months.  When  the  periosteum  is  extensively  torn, 
osteoblasts  wander  out  beyond  its  limits,  and  en- 
sheathing  callus  may  be  formed  in  quantity.  Much 
will  depend  on  the  amount  of  movement  to  which 
the  part  is  subjected.  Vigorous  movement,  or,  in 
those  cases  where  the  periosteum  is  stripped  away, 
deep  massage  applied  too  early  just  over  the  site  of 
the  fracture,  will  disseminate  the  osteoblasts  far  and 
wide.  Not  only  may  the  callus  be  excessive,  and, 
perchance,  lock  the  nearest  joint,  but  muscles,  nerves, 
or  tendons  may  become  ensheathed  b}^  new  bone, 
and  their  functions  be  impaired. 

Here  belong  those  interesting  and  by  no  means 
infrequent  cases  in  which,  after  a  fracture,  especially 
near  the  elbow-joint,  an  osseous  mass  develops  in  the 
muscles,  as  for  instance  in  the  brachialis  anticus. 
This  is  called  traumatic  myositis  ossificans.  The  mass 
can  be  moved  apart  from  the  bone,  and  casts  a 
shadow  with  the  x  rays.  What  has  happened  is  that 
massage  or  movements  have  scattered  the  osteoblasts 
far  and  wide,  and  they  have,  after  a  few  weeks, 
performed  their  usual  function,  and  regenerated  bone 
in  their  new  surroundings.  It  is  significant  that 
these  cases  have  become  common  only  since  the 
modern  treatment  by  massage  and  movements 
has  been  introduced,  excellent  as  it  is  when  suitably 
applied.  If  the  periosteum  had  remained  intact,  this 
could  never  have  occurred.  The  treatment,  if  such 
a  lump  forms,  is  not  excision,  which  usually  leads 
to  recurrence,  but  strict  limitation  of  movement  by 
means  of  a  splint. 


THE    GROWTH    OF    BONE  161 

The  reason  why  so  much  more  callus  forms  in 
animals  than  in  man  is  because  so  much  more 
movement  of  the  broken  ends  takes  place.  In  these 
circumstances  there  is  often  a  stage  in  which  cartilage 
is  to  be  found  in  the  callus,  on  its  way  to  form  bone. 

It  is  evident,  therefore,  that  care  should  be  exer- 
cised, after  a  fracture  in  which  it  is  probable  that  the 
periosteum  is  torn,  to  avoid  deep  massage  and  move- 
ments close  to  the  site  of  the  fracture  during  the  first 
fortnight,  although  they  may  well  be  applied  to  the 
neighbouring  joints.  When  the  fracture  is  very  near 
a  joint  it  is  far  better  to  trust  to  a  single  efficient 
movement  once  a  week  (to  avoid  adhesions)  than  to 
allow  repeated  small  movements  in  the  early  stages. 

It  is  well  known  that  exostoses  or  spurs  of  bone 
usually  form  in  the  attachment  of  muscles  or  tendons. 
The  probable  explanation  is  that  by  the  continual 
drag  and,  it  may  be,  sHght  wTenches,  some  osteo- 
blasts are  detached  from  the  bone  and  invade  the 
tendon. 

Universal  myositis  ossificans,  such  as  occurs  in  a 
so-called  'brittle  man',  may  be  due  to  some  such 
cause  as  this,  or  perhaps  to  embohsm  of  osteoblasts. 

The  strongest  evidence  for  the  older  \'iew,  that 
bone  is  laid  down  by  the  periosteum,  is  provided  by 
cases  of  acute  periostitis,  where  pus  forming  inside 
the  bone  finds  its  way  out  between  the  shaft  and  the 
periosteum,  so  that  the  latter  is  extensively  stripped 
up.  In  many  cases,  new  bone  begins  to  form  under 
the  detached  periosteum,  outside  the  pus,  and  the 
shaft  usually  necroses. 

Macewen    explains   this   occurrence    by   declaring 

11 


162  THE    GROWTH    OF    BONE 

that  if  the  inflammatory  mischief  is  not  very  acute, 
vasodilatation  takes  place  within  the  bone,  and  the 
osteoblasts  are  carried  out  by  the  Haversian  canals 
to  the  loose  areolar  space  under  the  periosteum,  to 
which  fibrous  membrane  some  of  them  adhere. 
When  this  is  stripped  up  later,  these  osteoblasts  lay 
down  new  bone,  but  those  remaining  on  the  shaft  are 
deprived  of  their  blood-supply  and  therefore  die.  If 
the  inflammatory  mischief  in  the  centre  of  the  bone 
is  very  acute,  the  whole  shaft  may  die,  especially  if 
thrombosis  occurs,  and  therefore  no  osteoblasts 
escape,  so  that  no  new  bone  at  all  can  be  laid  down 
under  the  periosteum.  This  is  by  no  means  a  rare 
occurrence. 

In  local  periostitis,  again,  which  should  rather  be 
described  as  an  osteitis,  the  bone-forming  cells  are 
brought  by  the  blood-stream  to  the  loose  areolar 
tissue  underneath  the  periosteum,  and  finding  there 
a  line  of  least  resistance,  are  able  to  lay  down 
young  bone,  and  so  produce  a  locahzed  swelling, 
marked  out  in  a  skiagram  by  a  faint  line  of  shadow 
close  to,  and  parallel  with,  the  shaft. 

The  truth  of  the  matter  probably  is  that  the 
active  osteoblasts  beneath  the  periosteum  in  normal 
bone  (the  cambium  layer)  may  adhere  either  to  the 
surface  of  the  bone,  or  to  the  under  surface  of 
the  periosteum,  under  different  circumstances  ;  in 
Macewen's  experiments  they  adhered  to  the  bone, 
and  this  is  probably  the  rule.  When  there  is 
inflammation,  and  the  periosteum  is  stripped  up  by 
pus,  many  of  them  prefer  to  stick  to  the  periosteum. 

During  operations  for  the  removal  of  bone,  great 


THE    GROWTH    OF    BONE  163 

efforts  are  often  made  to  preserve  the  periosteum, 
and  sometimes,  as  for  instance  in  excising  the  lower 
jaw,  the  membrane  is  preserved  even  at  the  risk  of 
leaving  septic  material  behind,  in  the  vain  hope  that 
it  will  form  new  bone.  The  only  possibility  of  its 
doing  so  is  if  osteoblasts  have  been  driven  out  by 
inflammation  and  have  become  adherent  to  it.  It  is 
useless  to  expect  healthy  periosteum  to  regenerate 
bone,  such  as  a  piece  of  rib  removed  for  empyema, 
though  it  may  form  a  guide  for  the  gap  to  be  filled 
by  growth  from  the  epiphyseal  end. 

Bone-grafting. — A  great  impetus  has  been 
given  to  the  study  of  these  problems  by  the  numerous 
opportunities  provided  by  war  surgery  for  bone- 
grafting.  Ununited  fractures  after  wounds  have 
been  of  common  occurrence,  and  the  surgeons  have 
all  been  busy  putting  bone-grafts  into  the  gaps.  At 
the  same  time,  the  Albee  operation  of  introducing  a 
bone-graft  from  the  tibia  into  a  furrow  in  the  split 
spinous  processes  of  the  vertebrae  for  Pott's  disease 
has  become  popular.  It  must  be  granted  that, 
whatever  the  technique,  our  experience  has  com- 
pletely established  the  fact  that  a  transplant  of 
living  bone  from  the  same  patient  (autogenous 
graft)  will  usually  Uve  and  grow  and  unite  firmly 
with  the  ends  of  the  bone  into  which  it  has  been 
introduced. 

There  have  been  very  many  histological,  skia- 
graphic,  and  other  studies  of  the  fate  of  the  graft, 
and  though  controversy  still  rages  between  the 
two  schools  as  to  the  part  the  periosteum 
plays   in    bone    regeneration,    one    may    begin    to 


164  THE    GROWTH    OF    BONE 

see  a  wa}^  of  reconciling  the  facts  on  the  one 
side  and  the  other.  It  is  quite  clear  that 
young  osteoblasts  can  reproduce  bone,  and  that 
old  ones,  shut  up  as  bone-corpuscles  in  lacunse, 
cannot.  Also,  we  know  that  bone  deprived  of 
periosteum  can  survive  and  form  a  useful  graft, 
uniting  with  the  ends  of  the  shaft  into  which  it 
is  ingrafted.  Nevertheless  its  periosteum  should 
always  be  preserved  if  possible,  because  the  Httle 
vessels  passing  from  the  periosteum  to  bone  are 
important  for  the  nutrition  of  the  bone,  and  the 
periosteum  readily  forms  vascular  connections  with 
the  surrounding  tissues.  Also,  the  most  active 
young  osteoblasts  are  found  principally  just  beneath 
the  periosteum,  and  on  the  surface  of  the  bone-shaft. 
Other  active  osteoblasts  hne  the  Haversian  canals 
and  the  lacunae  of  cancellous  bone,  and  are  especially 
numerous  in  the  endosteum,  that  is,  the  film  of  cells 
which  lines  the  bony  tube  surrounding  the  marrow 
cavity.  H  a  bone-graft  is  examined  microscopically 
some  months  after  the  operation,  the  great  bulk  of 
it  shows  dead  bone-corpuscles  and  some  absorption 
going  on,  but  beneath  the  periosteum  and  endosteum 
and  around  the  lacunas  there  is  li\ing,  growing  bone. 
The  success  of  a  bone-grafting  depends  also  on 
some  other  factors.  Asepsis  is,  of  course,  essential, 
and  so  is  secure  fixation  and  freedom  from  move- 
ment during  the  first  couple  of  months  or  so.  The 
permanence  and  strength  of  the  graft,  however, 
depend  on  the  use  that  is  made  of  it.  Function- 
less  bone,  buried  in  a  muscle  for  instance,  tends  to 
absorb ;    useful  bone,    filling  a  gap   in  the   j  aw  or 


THE    GROWTH    OF    BONE  166 

radius,  becomes  stronger  as  the  part  is  used.  Bone- 
grafts  into  the  femur  and  humerus  have  not  so  far 
been  successful. 

It  is  not  yet  decided  whether  rib-cartilage  will 
survive  well  and  function  as  a  graft.  I  have  used 
it  for  the  lower  jaw  and  also  for  closing  skull  gaps. 
It  has  two  advantages,  in  that  it  is  easy  to  work 
with  and  cut  to  shape,  and  that  normally  cartilage 
is  accustomed  to  a  scanty  blood-supply.  My  cases 
did  satisfactorily,  but  according  to  Leriche  and 
PoUcarde  the  hyaline  cartilage  part  of  the  graft  is 
slowly  absorbed. 

There  is  some  relationship,  not  well  understood, 
between  the  internal  secretions  of  the  ductless  glands 
and  the  growth  of  bone.  Over-secretion  of  the 
pituitary  gland,  as  we  shall  see,  results  in  overgrowth 
of  the  bones,  and  may  lead  to  gigantism.  On  the 
other  hand,  inadequate  thj^roid  secretion  will  stunt 
the  growth  of  the  bones,  as  is  seen  in  cretinism. 
Thyroid  medication  will  occasionally  lead  to  the 
consolidation  of  an  ununited  fracture,  or,  what  comes 
to  the  same  thing,  the  internal  secretion  of  the 
thyroid  gland  may  be  increased  by  giving  iodide  of 
potassium. 

REFERENCES. 
Macewen. — The  Growth  of  Bone,   Glasgow,   191 1. 
Hey     Groves,     Joll,     and     Wheeler. — Articles     '  Bone- 
grafts  ',  Med.  Annual,  1919. 


166 


CHAPTER    VIIl. 

THE    THYROID    AND     PARATHYROID 
GLANDS. 

HISTORY REMOVAL    OF    THE    THYROID    AND    PARATHYROIDS 

REMOVAL       OF       PARATHYROIDS       ALONE REISIOVAL       OF 

THYROID       ALONE THYROID       FEEDING — CHEMISTRY       OF 

THYROID       COLLOID — PARENCHYMATOUS       GOITRE — IODO- 
FORM AND  THYROIDISM ACTION  OF  IODIDES  ON  GUMMATA 

AND       ATHEROMA EXOPHTHALMIC         GOITRE PRACTICAL 

DEDUCTIONS. 

MUCH  of  the  clinical  and  experimental  work 
which  has  been  done  in  connection  with 
these  glands  can  no  longer  be  described  as  new,  but 
it  will  be  helpful  to  mention  in  passing  some  of  the 
well-known  results  obtained  by  the  first  observers. 

HISTORY. 

As  long  ago  as  1859,  Scliiff  described  the  fatal 
result  which  inevitably  supervenes  after  removal  of 
the  thyroid  gland  in  dogs,  but  it  was  not  until 
'  cachexia  strumipriva ',  or  operative  myxoedema, 
was  found  to  follow  so  man}^  of  Kochers  earh' 
operations  for  goitre  on  patients  coming  from  the 
goitrous  S\viss  valleys,  that  this  fact  attracted  much 
attention.  The  relation  of  the  thyroid  to  myxoedema 
was  then  established  by  Gull  and  Ord.  The  highly 
successful  treatment  of  myxoedema  and  cretinism  by 
thyroid  feeding  was  introduced  by  Murray,  follow- 
ing  on  the   observation   by   Schiff   and   subsequent 


THE    THYROID     GLAND  167 

workers  that  transplantation  of  the  gland  beneath 
the  skin  of  the  thyroidectomized  animal  relieved 
the  symptoms. 

REMOVAL    OF  THYROID   AND    PARATHYROIDS. 
We  will  consider  first  the  consequences  of  removal 
of   the   thyroid   gland   in    animals.      The   effect   of 
total  removal  varies  greatly  with  the  species.     Thus 
rodents  are  Httle  if  at  aU  affected,  sheep  and  cattle 
more  so;    in  man  and  monkeys  the  symptoms  are 
marked,  and  in  carnivores,  especially  foxes,  a  rapidly 
fatal  result  ensues.     To  some   extent  this   striking 
diversity  depends,  as  we  shall  see,  on  the  Hability  to 
simultaneous  removal   of   the   parathyroids;    for   a 
long  time  this  was  not  recognized.     Males  are  more 
severely   affected    than    females,  and    castration   is 
said   to   modify   the   symptoms.     Thyroidectomized 
animals  are  very  susceptible  to  cold,  and  keeping 
cats  warm  may  save  their  Hves  ;    of  course  thyroid 
medication  must  be  undertaken  at  the  same  time. 
It  is  weU  known  that  human  patients  \vith  myxoedema 
feel  the  cold  very  much.     The  symptoms  in  dogs 
and  monkeys   are   vomiting,   muscular   prostration, 
emaciation,  and  often  death.     Of  great  importance 
is  the  frequent  occurrence  of  tetany.     The  spasms 
are  at  first  slight,  affecting  the  jaw  muscles,  then 
they  spread  over  the  whole  body  and  may  be  fatal. 
Tliis   condition   has   several    times   foUowed   a   too 
extensive  removal  of  the  thyroid  in  man,  and  may 
also     occur     in     myxoedema.      Another     symptom 
present  frequently  in  monkeys  is  narrowing  of  the 
palpebral  fissure,  so-called  enophthalmos ;    we  shall 


168  THE    THTROIL)    AND 

see  that  administration  of  th^Toid  extract  may 
cause  exophthalmos.  True  myxoedema  is  not  often 
seen  in  the  experimental  animals.  It  has  been 
induced  in  mild  degree  in  monkeys  by  Horsley, 
Edmunds,  and  others,  but  not  with  any  constancy, 
and  in  other  animals  it  is  not  seen  at  all. 

It  is  not  usually  possible  to  save  the  Hves  of  dogs 
or  monkeys  whose  thyroids  have  been  removed, 
by  feeding  on  sheep's  th^^roid,  although  a  good  deal 
of  reUef  may  be  obtained  for  the  symptoms  in  this 
way.  Grafting  a  piece  of  the  gland  under  the  skin 
is  successful  for  a  while,  but  eventually  it  is  absorbed. 

The  effects  of  removal  of,  or  insufficient  secretion 
by,  the  thyroid  gland  in  man  are  myxcedema,  and 
occasionally  tetany. 

In  408  cases  in  Kocher's  cUnic  at  Beme  complete 
extirpation  of  the  thyroid  was  followed  by  myxoedema 
in  69  cases,  and  a  similar  operation  in  78  cases  in 
Billroth's  clinic  was  followed  by  tetany  in  13  cases, 
of  which  6  proved  fatal.  Feeding  with  sheep's 
thyroid  is  wonderfully  successful  in  myxoedema, 
but  is  not  usually  effectual  in  tetany. 

Partial  removals  of  the  thyroid  in  dogs  produce 
symptoms  of  correspondingly  lessened  severity. 
Halstead  found  that  in  one  case  one-eighteenth 
of  the  gland  sufficed  to  ward  off  symptoms  of 
athyroidism,  but  the  amount  which  could  safely  be 
left  varied  in  different  animals.  One  bitch  which 
had  lost  two-thirds  of  her  total  thyroid  became 
pregnant  by  a  healthy  male,  and  all  her  whelps  had 
enormous  goitres,  a  fact  which  has  also  been 
observed  by  Edmunds. 


PARATHYROID    GLANDS  169 

Histological  examination  of  the  portion  remaining 
shows  a  sequence  of  changes  remarkably  like  those 
occurring  in  exophthalmic  goitre,  namely,  distention 
and  irregular  shape  of  the  vesicles,  with  watery  fluid 
instead  of  colloid,  and  columnar  epithehum  instead 
of  cubical. 

REMOVAL     OF     PARATHYROIDS. 

The  variation  in  the  s^Tnptom-complex  following 
on  thyroidectomy,  and  the  variability  of  response 
to  thyroid  feeding,  both  depend  on  any  coincident 
injury  to  the  parath\Toid  glands.  For  many  years 
these  glands  passed  unrecognized,  and  most  of  the 
effects  attributed  above  to  removal  of  the  thyroid 
are  as  a  matter  of  fact  due  to  loss  of  the  parathyroids. 
These  are  two  pairs  of  small  glands,  about  one-third 
of  an  inch  long  and  usually  flattened  in  shape,  l}dng 
behind  the  lateral  lobes  of  the  thyroid  close  to  the 
trachea,  not  easUy  distinguishable  from  the  thyroid 
except  by  the  microscope,  when  they  are  seen  to 
consist  of  columns  of  polygonal  cells  with  no  regular 
arrangement  into  acini,  and  secreting  no  colloid. 
One  pair  was  discovered  by  Sandstrom  in  1880, 
and  the  functions  were  investigated  by  Gley  in 
1892  ;  but  the  second  pair  was  not  recognized  till 
Kohn's  monograph  appeared  in  1895.  A  number  of 
physiologists  have  since  described  the  effects  of 
removal  (Vassali  and  Generali,  Edmunds,  Moussu). 
If  all  four  parathyroids  are  taken  away,  the  animal 
succumbs  rapidly,  with  symptoms  just  such  as  have 
been  described  under  the  heading  of  thyroidectomy, 
tetany  being  a  marked  feature.     The  signs  are  the 


170  THE    THYROID    AND 

same  whether  the  thyroid  gland  is  removed  or  left. 
Lea\ang  one  parathyroid  is  usually  sufficient  to 
prevent  death,  but  tetany  may  still  ensue. 

Swale  Vincent  does  not  believe  in  the  relative 
importance  of  the  parathyroid  glands,  but  the 
evidence  is  so  weighty  and  so  well  supported  by 
many  observers  that  it  has  to  be  accepted. 

Changes  in  the  human  parathyroids  are  said  to  be 
very  frequent  in  cases  of  tetan}^  in  children  or 
pregnant  women,  and  also  in  osteomalacia,  in  which 
the  inorganic  matter  of  bone  is  largely  removed. 
There  are  facts  in  favour  of  the  hypothesis  that  the 
tetany  itself  depends  on  some  abnormality  of  the 
calcium  metabolism  of  the  body.  The  main  function 
of  the  parathyroid  glands  is  perhaps  to  control  the 
calcium  metabolism.  Normally  the  amount  of  cal- 
cium in  blood  serum  is  about  lo  mgrms.  in  lOO  c.c,  but 
in  spontaneously  occurring  tetany  it  sinks  to  about 
half  that  amount  (Howland  and  Marriott).  Calcium 
chloride  administration  raises  the  quantity  nearly 
to  normal,  and  rapidly  cures  the  spasms,  but  it  needs 
to  be  persisted  with  for  many  weeks. 

Noel  Paton  and  fellow  workers  at  Glasgow  believe 
that  the  symptoms  of  tetany,  whether  arising 
clinically  from  malnutrition,  chronic  colitis,  dilata- 
tion of  the  stomach,  etc.,  or  produced  experimentally 
by  excising  the  parathyroid  glands  in  animals,  are 
due  to  intoxication  with  a  chemical  substance  called 
guanidine,  which  gives  rise  to  identical  symptoms 
(tendency  to  spasms,  increase  in  muscular  tone,  rise 
in  the  non-urea-nitrogen  output  in  the  urine).  They 
quote   experiments,   which,    however,  do    not    seem 


PARATHYROID    GLANDS  171 

quite  conclusive,  that  go  to  show  that  guanidine  is 
present  in  the  blood  in  tetany.  According  to  this 
view,  the  function  of  the  parathyroid  tissue  is  to 
control  guanidine  metabolism.  It  is  not  clear  how 
the  calcium  theory  and  the  guanidine  theory  fit  in 
with  one  another. 

It  would  seem,  then,  that  in  man,  myx oedema  is 
due  to  loss  of  the  internal  secretion  of  the  thyroid 
itself,  but  that  tetany  and  fatal  symptoms  in  both 
man  and  animals  are  due  to  loss  of  the  parathyroids. 
The  convulsions  of  tetany  in  dogs  may  be  arrested 
by  feeding  on  a  watery  extract  of  twelve  to  twenty 
horses'  parathyroids  (Moussu). 

REMOVAL     OF     THYROID     ALONE. 

Removal  of  the  th^Toid  gland  without  the  para- 
thyroids is  usually  not  fatal ;  myxoedema  results 
in  man  ;  occasionally,  perhaps,  in  animals  also,  but 
more  commonly  only  cachexia.  In  young  animals, 
however,  the  results  are  much  more  distinctive, 
and  von  Eiselsberg  and  others  have  induced  very 
con\'incing  cretinism,  with  a  remarkable  stunting 
of  grov/th,  in  lambs,  goats,  rabbits,  and  asses.  It 
is  interesting  and  important  to  notice  that  the 
animals  so  treated  developed  exceedingly  marked 
atheroma  of  the  aorta,  of  which  von  Eiselsberg 
gives  good  figures. 

THYROID     FEEDING. 

We  now  turn  to  the  effects  of  thyroid  feeding  in 
the  normal  man  and  animal.  These  are  perfectly 
characteristic  if  large  doses  are  given.  The  blood- 
pressure  falls,  the  pulse  becomes  rapid  (120-140  or 


172  THE    THYROID    AND 

more),  there  may  be  fever,  headache  is  usual,  and 
there  is  great  mental  depression  or  excitement  in 
many  cases.  Exophthalmos  has  been  recorded 
several  times  after  an  overdose  in  man  (Beclere, 
Notthaft),  and  monkeys  (Edmunds).  The  metaboHc 
exchanges  of  the  body  are  increased,  consequently 
there  are  loss  of  weight  and  an  increased  output  of 
urea,  chlorides,  and  phosphates,  and  the  gaseous 
exchanges  in  the  lungs  are  above  normal  (Roos, 
Magnus  Levy).  It  will  be  noticed  that  the  parallel- 
ism with  Graves'  disease  is  very  striking. 

CHEMISTRY  OF  THYROID  COLLOID. 
Chemical  investigation  of  the  colloid  has  yielded 
some  important  results.  There  is  a  chemical  sub- 
stance called  iodothyrin,  which  has  the  characters  of 
a  globulin  (Oswald)  and  contains  a  variable  propor- 
tion of  iodine.  This  element  is  usually  abundant  in 
the  thyroid,  but  almost  absent  in  the  other  tissues 
of  the  body.  Its  presence  was  first  proved  by 
Baumann,  of  Freiburg,  in  1896,  and  has  been 
abundantly  confirmed  since.  The  amount  present 
Taries  with  the  species  and  also  with  the  individual ; 
in  some  cases  it  falls  below  the  limits  of  chemical 
recognition.  Herbivores  possess  it  in  abundance, 
most  vegetables  containing  iodine.  Orkney  sheep, 
which  feed  largely  on  seaweed  in  the  winter,  have 
an  extraordinary  amount.  In  carnivores  it  is  very 
scanty.  In  man  it  is  nearly  always  present  in 
recognizable  quantities,  except  in  young  children. 
Wells  finds  that  the  amount  varies  with  the  locality, 
and  in  general  is  inversely  in  proportion  to  the  local 


PARATHYROID    GLANDS  lia 

prevalence  of  goitre.  In  parenchymatous  goitre  the 
iodine  content  is  too  low  ;  in  exophthalmic  goitre  it 
is  too  high.  A  principal  function  of  the  thyroid  is 
to  control  the  iodine  metabolism  of  the  body. 

It  is  a  moot  point  whether  iodothyrin  is  the  active 
principle  of  the  thyroid  gland.  The  most  recent 
researches  suggest  that  it  is  not,  and  that  the 
amount  of  iodine  present  on  analysis  may  not  be  a 
rehable  indication  of  the  activity  of  a  gland 
extract.  On  the  other  hand,  Kendall  has  recently 
isolated  from  the  colloid  a  crystalline  indol  deriva- 
tive, rich  in  iodine,  to  which  he  gives  the  formula 
of  CnHjyO.jNI.5,  and  which  is  said  to  be  effectual 
in  curing  myxoedema  and  cretinism. 

PARENCHYMATOUS     GOITRE. 

Directing  our  attention  now  to  enlargements  of 
the  thwoid  gland,  we  rule  out  those  that  are  merely 
due  to  tumour  formation,  such  as  adenoma  or  cystic 
disease,  and  confine  ourselves  to  the  parenchyma- 
tous goitres.  It  has  long  been  known  that  there  is 
some  connection  between  drinking-waters  and  the 
incidence  of  goitre.  The  disease  is  extraordinarily 
prevalent  in  certain  districts,  and  especially  where 
the  water-supply  is  derived  from  particular  geological 
formations,  such  as  the  molasse  in  S\sitzerland 
and  the  carboniferous  limestone  in  Derbyshire.  In 
Khokand,  Turkestan,  a  very  large  proportion  of 
the  whole  population  suffers,  and  Russian  soldiers 
stationed  there  rapidly  acquired  the  disease.  The 
introduction  of  a  new  water-supply  has  several  times 
induced  an  epidemic  of  goitre  in  a  town,  or,  on  the 


174  THE    THYROID    AND 

other  hand,  reduced  the  number  of  cases  in  an 
endemic  area.  Thus  at  Rupperswyl,  near  Aarau, 
an  endemic  area  in  which  59  per  cent  of  the 
children  were  goitrous,  in  1884  the  water-supply  was 
changed  for  one  from  a  non-goitrous  district,  and 
in  ten  years  the  percentage  had  fallen  to  eleven. 
There  are  on  the  Continent  certain  goitre  wells  called 
Kropfbrunnen,  at  which  young  men  anxious  to 
escape  conscription  drink.  They  have  been  known 
for  centuries,  and  the  water  wall  induce  goitre  in 
horses  and  dogs,  as  well  as  in  man.  Boiling  the 
water  destroys  its  remarkable  effect  on  the  thyroid 
gland.  This  has  been  taken  to  prove  that  some 
hving  organism  is  the  effective  cause,  but  another 
theory  is  more  probable,  as  we  shall  see  later. 

During  Captain  Cook's  vo3^age  in  1772,  it  is  related 
that  the  crew  ran  short  of  water,  and  had  recourse  to 
blocks  of  ice  from  the  icebergs  amongst  which  they 
were  sailing,  melting  them,  in  iron  pots.  Quite  a 
number  of  those  who  partook  of  this  water  developed 
a  goitre,  other  members  of  the  crew  escaping. 

A  large  projecting  sweUing  of  the  thyroid  is  not 
uncommon  in  trout  kept  in  certain  tanks  or  streams. 

In  the  earher  stages,  parenchymatous  goitre  can 
usually  be  cured,  either  by  feeding  on  thyroid  extract 
or  by  means  of  potassium  iodide.  Marine*  has 
pointed  out  that  in  America  there  was  formerly  a 
serious  commercial  loss  in  some  districts  from  cretin 
lambs,  and  that  sheep  and  dogs  with  goitre  were 
numerous ;    the  substitution   of    an   iodiferous   salt 

*  Johns  Hopkins  Hosp.  Bull.,  1907,  xviii,  p.  359. 


PARATHYROID    GLANDS  175 

for  pure  rock-salt  has  been  completely  successful 
in  preventing  all  these  manifestations. 

Chalmers  Watson,  and  more  recently  Edmunds, 
have  obtained  goitre  in  fowls  by  a  meat  diet.  The 
low  iodine-content  of  the  meat  makes  it  necessary 
for  the  thyroid  to  enlarge,  so  as  to  take  the  greatest 
advantage  of  what  iodine  it  can  get. 

There  is  abundant  evidence  that  iodides,  and 
especially  organic  combinations  of  iodine  such  as 
iodoform,  have  great  power  in  enhancing  the 
activity  of  the  th}TCtid  gland.  We  have  already 
seen  that  the  gland  normally  secretes  iodine  into  the 
blood-stream,  combined  with  a  globulin.  Roos, 
and  more  recently  Hunt  and  Seidel,  have  shown 
that  the  activity  of  the  colloid  varies  directly  with 
the  amount  of  iodine  contained  in  it,  but  this  is  not 
imiversally  accepted.  WTien  iodides  or  iodoform  are 
given  by  the  mouth,  they  are  taken  up  by  the  thyroid 
and  secreted  in  the  blood-stream  in  the  form  of  iodo- 
thyrin,  which  may  be  the  normal  active  principle 
of  the  gland.  The  amount  of  iodine  in  the  gland  in 
these  circumstances  rises  considerably,  as  has  been 
proved  by  Oswald  in  man,  and  by  Hunt  and  Seidel 
in  dogs. 

What,  then,  is  the  relation  between  iodine 
metabolism  and  goitre  ? 

In  the  first  place,  we  may  conclude  that  the 
thjToid  enlarges  in  goitre  because  it  is  necessary 
for  it  to  do  increased  work.  A  certain  quantity  of 
iodothyrin  is  needful  for  the  general  well-being  of  the 
individual ;  if  the  gland  is  scantily  supplied  with 
iodine,  it  must  enlarge  in  order  to  take  the  fullest 


176  THE    THYROID    AND 

possible  advantage  of  all  that  may  be  brought  to 
it  by  the  blood-stream.  In  the  same  way  a  kidney 
hypertrophies  when  its  fellow  is  degenerated,  in  order 
to  obtain  more  urea  for  excretion ;  and  the  red  blood- 
corpuscles  double  in  number  when  a  man  takes  up 
his  abode  in  the  rarefied  atmosphere  of  great  alti- 
tudes, to  make  the  best  use  of  the  diminished  supply 
of  oxygen.  It  has  been  shown  by  Oswald  in  a  number 
of  observations  that  in  goitre  the  thyroid  colloid  is 
exceeding^  deficient  in  iodine,  both  in  calves  and 
man.  Thus  we  get  a  clue  to  the  successful  treatment 
of  the  affection  either  by  iodiferous  compounds 
or  by  thyroid  extract.  It  is  weU  known  that  either 
of  these  remedies  will  cure  early  cases  of  goitre, 
before  the  enlargement  becomes  chronic.  The 
success  of  the  iodiferous  rock-salt  on  the  American 
farms  may  be  accounted  for  in  the  same  way.  An 
explanation  is  also  offered  of  the  fact,  noticed 
previously,  that  the  whelps  of  bitches  from  whom 
a  good  part  of  the  thyroid  has  been  removed  are 
all  goitrous,  the  plasma  supphed  to  the  foetal  glands 
e\ddently  containing  a  deficiency  of  iodine  derived 
from  the  maternal  thyroid.  Of  2333  cases  of  con- 
genital goitre  collected  by  Fabre  and  Thevenot,*  the 
mother  was  almost  invariably  goitrous.  The  foetal 
thyroid  enlarges  in  order  to  obtain  as  much  iodine 
as  it  can. 

It  was  natural  to  suggest  that  the  waters  of  the 
Kropfbrunnen  were  deficient  in  iodine,  but  this 
theory  would  overlook  the  fact  that  the  bulk  of  our 

*  Revue  de  Chirurgie,  190S,  June  10. 


PARATHYROID    GLANDS  177 

iodine  is  derived  from  vegetables,  not  from  drinking- 
water,  and  as  a  matter  of  fact  these  wells  show 
no  constant  deficiency  or  excess  of  iodine.  It  is 
possible  that  they  contain  minute  traces  of  some 
metal  having  a  great  affinity  for  iodine,  and  forming 
with  it  an  insoluble  compound.  It  is  quite  conceiv- 
able that  boiling  the  water  might  precipitate  such 
a  metal.  This,  if  taken  into  the  body,  would  with- 
draw so  much  of  the  available  iodine  as  inert  metallic 
iodide,  that  the  thyroid  must  enlarge  to  obtain  the 
indispensable  minimum. 

Major  McCarrison,  who  has  been  observing  endemic 
goitre  amongst  the  Gilgit  highlands  in  North  India, 
has  lately  brought  forward  fresh  arguments  in  favour 
of  a  bacteriological  theory  of  its  causation.  He  has 
induced  a  definite  swelhng  of  the  thyroid  both  in 
himself  and  in  natives  by  drinking  the  muddy  residue 
on  the  filter  ;  the  filtered  water,  in  a  short  experi- 
ment, did  not  give  rise  to  goitre,  nor  did  boiled  water. 
No  organism  could  be  found  in  punctures  of  the 
gland.  Goats  given  water  to  drink  contaminated  by 
the  fasces  of  goitrous  patients,  in  some  cases,  though 
not  in  others,  developed  a  certain  amount  of  swelling 
of  the  thyroid  gland,  and  in  man  ten-grain  doses  of 
thymol,  used  as  an  intestinal  antiseptic,  reduced  the 
size  of  a  goitre  in  some  patients.  Hence,  McCarrison 
beheves  that  the  disease  is  due  to  an  intestinal 
organism.  According  to  Wilms,  Bircher,  and  others,* 
the  water  of  goitre  wells  retains  the  power  of  inducing 


*  Bircher,  Deut.  vied.  Wochensch.,  1910,  No.  37  ;  Wilms,  Deui. 
ined.  Wochensch.,  igio,  No.  13  ;  Koile.  Korrespond.  j.  schweiz. 
Aerzte,  1909,  No.  17. 

12 


178  THE    THYROID    AND 

thyroid  enlargement  in  rats  after  passing  through  a 
Berkefeld  filter.  It  is  true  that  a  few  tiny  bacteria 
are  filter-passers,  but  the  immense  majority  are  held 
back.  It  is  easy  to  cause  enlargement  of  the  thyroid 
by  various  means  ;  Bircher  shows  that  food  con- 
taminated by  the  faeces  of  normal  rats  causes  goitre 
in  other  rats. 

There  are  goitre  wells  in  England.  One  is  known 
to  the  writer  near  Berkeley,  in  Gloucestershire. 
Its  water  is  used  by  only  one  or  two  families,  but 
four  cases  of  goitre  have  resulted.  It  is  usually  the 
growing  children  who  suffer. 

IODOFORM     AND     THYROIDISM. 

The  conclusions  which  modern  phj-siology  has 
reached  with  regard  to  the  relation  between  iodine 
compounds  and  the  thyroid  gland  lead  us  to  some 
further  important  explanations  of  obscure  problems. 
We  are  now  able  to  understand  the  toxic  effects  of 
iodoform,  and  the  beneficial  action  of  iodides  on 
arteriosclerosis,  aneurysm,  and  gummata. 

Iodoform  poisoning  has  become  a  well-recognized 
condition,  and  every  text-book  on  pharmacology  or 
toxicology  gives  a  clear  description  of  the  chnical 
picture,  which  the  writer  has  verified  by  consulting 
the  reports  on  some  lOO  cases  scattered  through 
the  literature,  not  including  the  very  numerous 
records  of  dermatitis  or  erythema  following  its  local 
use.  A  long  list  of  well-described  cases  (not  always 
very  convincing)  is  given  by  Cutler.* 

*  Boston  Med.  Soc.  Journal,  1886,  ii,  pp.  73,  loi,  no. 


PARATHYROID    GLANDS  179 

There  are  four  main  varieties  of  iodoform  poi- 
soning : — 

1.  Skin  eruptions,  such  as  dermatitis,  erythema, 
and  swelling. 

2.  Persistent  subjective  taste  and  smell  of  the 
drug  long  after  its  application  has  been  discontinued. 

3.  Toxic  amblyopia  (5  cases),  and  optic  atrophy 
(i  case). 

4.  Acute  thyroid  symptoms,  comprising  rapid 
pulse,  delirium,  headache,  vomiting,  and  a  variable 
amount  of  fever.  The  most  characteristic  sequence 
is  when  the  pulse  is  very  rapid  but  the  temperature 
normal. 

Of  the  above  groups  we  are  now  concerned  only 
with  the  last. 

It  will  be  noticed  that  the  clinical  picture  cor- 
responds exactly  to  that  seen  after  administration 
of  excessive  doses  of  thyroid  extract.  Iodoform 
causes  its  toxic  effects  by  stimulating  the  internal 
secretion  of  the  thyroid  gland,  with  the  production 
of  acute  thyroid  intoxication. 

I  have  described  a  case  in  which  chronic  thyroid 
intoxication,  that  is  to  say  Graves'  disease,  clearly 
followed  the  application  of  iodoform  to  an  absorbing 
surface.  There  was  certain  proof  that  too  much 
iodoform  was  absorbed,  because  for  weeks  after  the 
drug  had  been  withdrawn  the  patient  was  haunted 
by  its  smell  and  taste.  The  tachycardia  and  wasting 
were  first  noticed  a  week  or  two  after  this  symptom 
developed.  The  Graves'  disease  was  still  present  in 
a  mild  form  one  year  later,  but  eventually  disappeared. 

Hunt   and  Seidel  have   shown  that   after  dosing 


180  THE     THYROID     AXD 

a  dog  with  iodofonn,  the  iodine  content  and  the 
acti\'ity  of  the  th3Toid  colloid  are  both  increased 
greatly.  The  thyroid  secretes  into  the  blood,  as 
iodothyrin,  the  iodine  derived  from  the  iodoform. 
\\Tien  strychnine  is  excreted  by  the  kidneys  the 
excretion  is  merely  discharged  from  the  body,  and 
therefore  the  drug  can  do  no  more  harm.  But  the 
increased  secretion  of  the  thyroid  is  discharged  not 
externally  but  into  the  blood,  and  may  poison  the 
patient. 

ACTION     OF     IODIDES     ON      GUMMATA     AND 
ATHEROMA. 

A  similar  increase  in  the  thyroid  secretion  may 
be  obtained  by  giving  iodides,  but  apparently  the 
gland  is  not  able  to  utilize  these  as  readily  as  it  does 
iodoform,  for  large  doses  do  not  so  easily  cause 
acute  thyroid  intoxication.  Here  we  find  the  ex- 
planation, so  long  sought  in  vain,  of  the  effect  of 
iodides  on  gummata,  arteriosclerosis,  and  aneurysm. 
The  beneficial  agent  is  really  the  increased  internal 
secretion  of  the  thyroid  gland. 

Two  important  results  of  obser\"ation  and  experi- 
ment confirm  this  theory. 

In  the  first  place,  in  cases  of  myxoedema,  arterio- 
sclerosis is  earh^  and  intense.  The  same  is  true  in 
animals  after  removal  of  the  thyroid.  \'on  Eiselsberg 
gives  a  number  of  very  convincing  photographs  of 
intense  atheroma  of  the  aorta  in  his  cretin  lambs 
in  which  the  thyroid  had  been  removed  in  early  life. 
In  the  second  place,  thyroid  extract  has  a  wonderful 
power  over  young  connective  tissue,  as  is  seen  by  the 


PARATHYROID    GLANDS  181 

way  in  which  it  absorbs  the  subcutaneous  thickening 
of  myxoedema  and  cretinism.  It  is  not  surprising, 
therefore,  that  it  should  be  able  to  deal  also  with 
gummata  and  atheroma.  By  its  absorptive  effect 
on  the  atheroma,  it  may  work  some  improvement  in 
aneurysm. 

I  have  found  th\Toid  extract  quite  as  effectual  a? 
iodide  of  potassium  in  heahng  tertiary  syphilitic 
ulcers. 

EXOPHTHALMIC     GOITRE. 

The  arguments  in  favour  of  the  hypersecretion 
theor\-  of  this  disease  appear  to  almost  all  observers 
to  be  of  oven.vhelming  strength.  The  th3Toid 
gland  is  enlarged,  vascular,  and  soft  in  most  cases ; 
occasionally  it  is  normal  in  size.  Microscopically, 
the  acini  are  dilated  and  irregular,  and  the  contents 
too  water}'.  These  are  just  the  changes  seen  in  the 
actively  secreting  fragment  left  after  a  sub-total 
th}Toidectomy.  The  colloid  contains  too  much 
iodoth\Tin  as  compared  with  the  normal  gland. 
The  wasting,  restlessness,  and  quick  pulse  may  all 
be  reproduced  w*ith  constancy  in  man  or  animals 
by  thyroid  feeding,  and  exophthalmos  has  also  been 
obtained  occasionally  in  both  man  and  the  monkey. 
The  underhdng  cause  of  the  hypersecretion  is  still 
unknown.  A  few  cases  may  be  lighted  up  by  fright 
or  by  iodoform  poisoning. 

Emotional  storms  such  as  terror,  anger,  intense 
mental  conflict,  and  the  like,  undoubtedly  produce 
an  increased  outpouring  into  the  blood  both  of  ad- 
renalin and  of  the  internal  secretion  of  the  thyroid 


182  THE    THYROID    AND 

gland,  and  it  has  been  suggested  that  some  of  the 
cases  of  nervous  instabihty  and  rapid  pulse  with 
some  dilatation  of  the  heart  occurring  in  soldiers 
after  very  anxious  experiences,  prolonged  over  weeks 
or  months,  may  be  due  to  hyperthyroidism  (Johnson) . 
In  a  few  cases  a  transient  exophthalmos  has  been 
observed. 

PRACTICAL     DEDUCTIONS. 

We  may  seek  here  to  sununarize  the  conclusions, 
in  so  far  as  they  are  of  importance  to  the  cHnician, 
that  the  New  Physiology  has  reached.  We  leam 
that  parenchymatous  goitre  is  a  hypertrophy  of 
the  thyroid  gland,  designed  to  enable  it  to  obtain 
sufficient  iodine  from  the  blood,  this  element  being 
an  essential  constituent  of  its  internal  secretion. 
The  deficiency  in  iodine  is  in  some  comphcated  way 
connected  \\^th  the  drinking-water.  In  the  early 
stages,  iodides,  thjnroid  feeding,  or  probably  iodo- 
form will  work  improvement,  and  the  water  should 
be  boiled,  or  the  supply  changed.  Should  operative 
measures  be  adopted,  we  leam  that  the  whole  gland 
must  not  be  removed,  or  myxoedema  may  result, 
and  that  the  four  small  parathyroids  King  behind 
it  must  also  be  respected,  or  the  patient  may  develop 
tetan5^  In  some  cases  the  loss  of  the  parathyroids 
on  one  side  only  has  caused  this  unpleasant  sequel. 
An  attempt  should  therefore  be  made,  in  removing 
one  lobe  of  the  thjToid  for  goitre  or  adenomata,  to 
leave  these  little  glands  intact  and  in  situ,  and  to 
preserv^e  their  blood-supply.  They  will  not  be 
injured  if  the  posterior  part  of  the  capsule  of  the 
thyroid  is  left. 


PARATHYROID    GLANDS  188 

If  myxoedema  or  tetany  do  follow  the  operation, 
they  may  be  remedied  by  thyroid  and  parath>Toid 
feeding  respective!}'.  There  is  some  evidence  that 
even  the  medical  varieties  of  tetany  are  due  to  loss  of 
the  internal  secretion  of  the  parathyroids  ;  according 
to  Kocher,  this  has  been  proved  in  the  case  of  the 
tetany  of  pregnancy,  and  other  obser\^ations  have 
since  been  made  in  which  the  parathyroids  were 
diseased  when  tetany  was  present.  Parathyroid 
feeding  should  therefore  be  worth  a  trial  in  such 
cases  also.  Macallum*  recommends  the  adminis- 
cration  of  calcium  salts,  or  milk,  which  is  rich  in 
calcium  salts.  He  has  sho\\Ti  experimentally,  and 
Edmunds f  has  confirmed  the  statement,  that  these 
salts  will  cure  tetany.  Thyroid  and  parathyroid 
grafting  have  both  been  undertaken  in  man  for 
cretinism  and  tetany  respectively,  with  the  idea  of 
reheving  the  patient  from  the  necessity  of  taking 
drusfs  all  his  davs.  In  a  few  cases  success  has 
resulted,  but  unfortunately  the  graft  becomes 
absorbed  as  a  general  rule,  and  soon  ceases  to 
function. 

In  a  case  recently  described  by  Brown,  of 
Melbourne,  parath\Toid  feeding  and  calcium  salts 
both  failed  to  reheve  tetany  in  a  patient  who  had 
been  treated  by  a  too  extensive  thyroidectomy  for 
Graves'  disease.  The  in-grafting  of  parath>Toid 
tissue  from  dogs  and  monkeys  gave  pronounced  relief 
for  about  twelve  days,  but  she  relapsed  after  each 


*  Journal  of  Experimental  Med.,  New  York,  1909,  vol.  xi,  p.  118. 
t  Journal  of  Path,  and  Bad.,  1910,  p.  288. 


184  THE    THYROID    AND 

operation.  Human  parathyroid  was  then  grafted, 
and  the  cure  seemed  to  be  permanent.  I  have  seen 
a  case  apparentl}^  cured  by  the  grafting  of  human 
parathyroid. 

We  see  also  that  exophthalmic  goitre  is  due  to 
hypersecretion,  as  is  proved  by  the  artificial  imita- 
tion of  the  disease  by  excessive  thjToid  feeding,  by 
the  excess  of  iodine  present  in  the  colloid  in  Graves' 
disease,  and  by  the  character  of  the  histological 
changes.  Thus  we  have  reason  to  expect  good  from 
partial  removal,  which  has  been  very  successful  in 
the  hands  of  Kocher,  the  Mayos,  and  others.  More 
than  half  the  gland  needs  to  be  excised.  It  would 
be  reasonable  also  to  try  the  effect  of  iodine  starva- 
tion, by  eliminating  vegetables  and  ordinary  tap- 
water  from  the  dietary,  and  substituting  for  the 
latter  the  water  of  a  goitre  well.  It  is  well  known 
that  exophthalmic  goitre  and  parenchymatous  goitre 
show  a  sort  of  geographical  antagonism,  and  the 
effect  of  the  water  in  reducing  the  amount  of  iodine 
available  for  conversion  into  iodothyrin  would  be 
valuable. 

Further,  we  are  helped  to  understand  and  to 
recognize  cases  of  iodoform  poisoning,  and  to  learn 
caution  in  the  use  of  this  drug  on  absorbing 
surfaces.  It  is  safer  in  children  than  in  adults, 
possibly  because  the  thyroid  in  children  contains 
less  iodine.  It  ought  not  to  be  used  in  patients 
who  have  ever  shown  a  tendenc}^  to  thyroidism, 
lest  acute  poisoning  or  an  attack  of  Graves'  disease 
be  precipitated. 

Finally,  we  obtain  a  clue  at  last  to  the  remarkable 


rARATHVROID     GLANDS  185 

action  of  iodides  in  arteriosclerosis  and  gummata, 
and  it  is  reasonable  to  hope  that  organic  compounds 
of  iodine,  which  cause  acute  thyroidism  more  readily 
than  the  alkahne  salts,  may  be  yet  more  effectual 
in  stimulating  the  activity  of  the  thyroid  gland.  In 
fact,  thyroid  extract  itself  may  prove  to  be  the 
best  remedy  of  all. 

REFERENCES. 

Richardson,  —  The  Thyroid  and  Parathyroid  Glands. 
Philadelpliia,   1905, 

Hunt  and  Seidel. — "  Studies  on  Thyroid",  Hygienic  Labor- 
atory Bulletin  of  Public  Health,  Washington,  igog. 

Rendle    Short. — Bristol  Med.-Chir.  Jour.,   1910,  p.   122. 

McCarrison. — Lancet,   1913,  i. 

Noel  Paton. — Jour.  Exper.  Physiol.,  1916,  x,  pp.  203,  382. 

Johnson.. — Brit.   Med.  Jour.,    1919,  i,  p.  335. 

Rowland   and  Marriott. — Quart.  Jour.  Med.,  19 18,  p.  289 

Kendall. — Jour.  Amer.  Med.  Assoc,  lx\'i,  1916,  p.  811. 


1S8 


CHAPTER    IX, 
THE  PITUITARY  AND   PINEAL  GLANDS- 

STRUCTURE  Or  THE  PITUITARY — THE  EFFECTS  OF  REMOVAL 
IN  ANIMALS INJECTION  OF  EXTRACTS PITUITARY  FEED- 
ING  ACROMEGALY    AND    GIGANTISM FROHLICH'S    TYPE 

FUNCTIONS      OF      THE      PITUITARY     GLAND THERAPEUTIC 

VALUE    OF   PITUITARY    EXTRACT — THE    PINEAL    GLAND. 

THE  pituitar}^  gland  consists  of  three  portions, 
the  pars  anterior,  which  is  epitheUal  in  structure, 
the  pars  intermedia,  also  consisting  of  epithelium 
and  varying  much  in  different  animals,  and  the  pars 
nervosa,  made  up  of  neuroglia  cells  and  fibres. 

The  pars  anterior  is  glandular,  consisting  of 
columns  of  epithelial  cells  which  in  young  animals 
may  line  tubules  ;  later  the  lumen  disappears.  It 
shows  three  different  types  of  cells,  with  eosinophile, 
basophile,  or  chromophobe  protoplasm,  whereof  the 
last  are  ordinarily  few  and  inconspicuous,  and  do 
not  take  the  stains.  There  may  also  be  masses  of 
basophile  colloid  between  the  cells,  especially  near 
the  pars  intermedia.  According  to  Blair  Bell,  the 
eosinophile  cells  are  the  normal  active  secretory- 
cells,  the  basophile  form  a  storage  secretion,  the 
small  chromophobes  are  exhausted  cells,  and  the 
large  chromophobes,  which  are  abundant  in  preg- 
nancy and  may  take  the  eosin  stain  faintly,  are 
only  met  with  when  there  is  an  excessive  demand  for 
pituitany''  secretion. 


PITUITARY    AND    PINEAL    GLANDS    187 

The  pars  intermedia  is  poorly  developed  in  man, 
extensive  in  the  dog  and  cat.  It  consists  of  epithelial 
cells,  faintly  basophile,  with  a  good  deal  of  colloid, 
which  may  be  eosinophile  or  basophile. 

There  is  often  a  cleft  separating  the  pars  anterior 
and  the  pars  nervosa.  The  whole  gland,  and  especi- 
ally the  epithelial  parts,  is  very  vascular.  In  the 
cat  the  pars  nervosa  has  a  central  cavity  opening 
into  the  third  ventricle. 

The  pars  anterior  and  pars  intermedia  are  derived 
from  a  pit  in  the  dorsal  wall  of  the  pharynx  ;  the 
pars  nervosa  is  budded  out  from  the  brain,  and  the 
stalk  persists. 

All  the  ductless  glands  are  studied  by  four  methods. 
We  have  to  find  the  effects,  firstly,  of  removal  in 
animals  ;  and  secondly,  of  the  injection  or  ingestion 
of  extracts.  We  have,  thirdly,  to  make  chemical 
analyses  of  the  extracts,  to  isolate  any  active  principle. 
Finally,  a  clinical  study  of  symptoms  in  man  associ- 
ated with  any  abnormalities  of  the  gland  may  be 
expected  to  throw  a  light  on  the  problem,  and  the 
effect  of  treating  these  conditions  will  also  need  to 
be  known. 

These  are  here  set  forth  in  the  rational,  not  in 
the  historical,  order.  It  may  be  said  at  once  that 
the  active  principle  or  principles  have  not  yet  been 
isolated. 

THE    EFFECTS    OF    REMOVAL    OF    THE 
PITUITARY    GLAND    IN     ANIMALS. 

It  is  so  difficult  to  remove  the  organ  from  its  well- 
concealed   nest    that    the   earlier   published   results 


188  THE     PITUITARY    AND 

inspired  no  confidence.  It  was  said  that  the  animals 
died,  but  the  injury  to  vital  structures  was  necessarily 
great,  and  it  has  been  remarked  that  the  result 
would  probably  have  been  equally  fatal  if  the 
operator  had  removed  the  dorsum  sellae  instead  of  the 
gland  !  But  the  careful  and  repeated  observations 
of  Paulesco  on  twenty-two  animals,  and  of  Gushing 
and  his  co-workers  on  about  two  hundred  dogs, 
have  completely  established  confidence  in  the  state- 
ments now  before  us. 

It  is  proved  that  removal  of  the  anterior  lobe  alone, 
in  dogs,  produces  just  as  much  effect  as  removal  of 
the  whole  gland,  but  that  a  removal  hmited  to  the 
posterior  lobe  causes  no  symptoms  at  all. 

The  animal,  after  a  total  removal,  shows  no 
deviation  from  the  normal  for  a  period  varving  from 
thirty-six  hours  to  two  weeks  after  the  operation. 
Then  it  becomes  unsteady,  there  is  arching  of 
the  back,  low  temperature,  shivering,  and  death 
in  unconsciousness.  Achsner,  Handelsmann  and 
Horsley,  Morawski  and  others,  find  that  death  is 
by  no  means  inevitable  after  enucleation  either  of 
the  anterior  lobe  or  the  whole  gland,  and  if  we 
could  be  sure  that  they  had  not  left  part  of  the 
organ  behind,  the  positive  evidence  of  survivals 
must  outv/eigh  statements  to  the  contrary.  The 
carefully  described  experiments  of  Blair  Bell  confirm 
Gushing' s  observations  that  removal  of  the  whole 
gland  or  pars  anterior  is  fatal,  and  removal  of  the 
pars  nervosa  innocuous. 

Gushing   has    found   it   possible   to   effect   partial 
removals  of  the  gland.     In  young  animals,  the  result 


PINEAL    GLANDS  189 

is  that  an  '  infantile  '  type  is  maintained,  and  the 
secondary  sexual  characters  do  not  develop.  In 
older  animals,  the  genitals  atrophy,  and  they  get  very 
fat.  He  gives  ver\'  convincing  photographs  showing 
that  these  changes  are  quite  marked.  Blair  Bell 
found  very  Httle  change  except  drowsiness  and  a 
variable  degree  of  atrophy  of  the  female  genital 
organs  after  partial  removals  of  the  pars  anterior, 
but  in  two  cases  he  obtained  adiposity  and  genital 
atrophy  in  marked  degree  by  compression  or  separa- 
tion of  the  stalk.  One  of  his  specimens  is  in  the 
Museum  of  the  Royal  College  of  Surgeons.  Probably 
the  effect  is  due  to  interference  with  the  blood-supply 
of  the  whole  gland. 

Another  consequence  is  a  remarkable  influence 
upon  the  metaboUsm  of  sugar.  It  is  well  known  that 
removal  of  the  pancreas  causes  gh'cosuria.  Partial 
removal  of  the  pituitary,  on  the  other  hand,  causes  an 
increased  power  of  warehousing  sugar  in  the  body. 
In  man,  if  more  than  150  grms.  of  glucose  ^are 
taken  at  a  dose,  some  \\ill  overflow  in  the  urine.  If 
the  action  of  the  pituitary  was  subnormal,  judging 
by  the  results  of  animal  experiments  and  a  few 
observations  on  man,  even  a  larger  dose  than  this 
would  not  cause  glycosuria. 

Stimulation  of  the  superior  cervical  s\'mpathetic 
ganghon  causes  glycosuria  in  the  rabbit,  cat,  or  dog. 
This  occurs  if  all  do\Mi-running  nerves,  such  as  the 
vagi,  are  blocked,  but  is  abolished  by  previous 
removal  of  the  posterior  lobe  of  the  pituitary.  These 
experiments  (Weed,  Gushing,  and  Jacobson)  support 
the    view   that    the   pars   nervosa   has   an   internal 


190  THE    PITUITARY    AND 

secretion  that  turns  glycogen  into  glucose,  and  that 
this  internal  secretion  is  controlled  by  the  sympa- 
thetic nervous  system. 

There  is  some  obscure  connection,  not  only 
between  disease  or  removal  of  the  pituitary  and 
the  genital  glands,  but  also  between  the  pituitary 
and  the  thyroid.  Thyroidectomy  leads  to  all  the 
signs  of  excessive  activity  in  the  pituitary. 

INJECTION  OF  EXTRACTS  OF  PITUITARY  GLAND. 
PITUITARY    FEEDING. 

Injection  of  extracts  of  the  anterior  lobe  causes 
no  evident  results.  Injection  of  extracts  of  the 
posterior  or  nen,"ous  lobe  causes  quite  constantly  a 
prolonged  rise  of  blood-pressure.  Not  only  the  blood- 
vessels, but  all  varieties  of  unstriped  muscle,  are 
stimulated  to  contract.  Peristaltic  movements  are 
set  up  in  the  bowel,  and  the  bladder  and  uterus, 
whether  pregnant  or  not,  also  contract. 

Prolonged  pituitary  feeding  in  animals  leads  to 
great  emaciation.  It  was  originally  stated  by 
Schafer  that  young  rats  showed  an  exaggeration  of 
growth  when  fed  with  this  gland,  but  repetition  of 
the  experiment  by  himself  and  others  does  not  con- 
firm this. 

Pituitary  extract  also  stimulates  the  flow  of  milk 
in  animals,  but  it  is  not  yet  proven  that  it  does  so 
in  the  human  subject.  It  appears  probable  that  the 
effect  is  merely  due  to  contraction  of  the  unstriped 
muscle  in  the  nipple  ducts  squeezing  out  secretion. 

Extract  of  the  pars  nervosa  is  also  a  powerful 
diuretic. 


PINEAL     GLANDS  191 

CLINICAL     RESULTS     OF    LESIONS    OF    THE 
PITUITARY     GLAND. 

It  is  well  known  that  the  somewhat  rare  diseases 
acromegaly  and  gigantism  are  general!}^  but  not 
quite  invariably  associated  with  enlargement  of 
the  pituitary  gland,  which  has  usually  been  a  simple 
overgrowth,  although  later  adenoma  or  fibrosis  may 
have  developed.  Whether  acromegaly  or  gigantism 
will  result  appears  to  be  principalh^  a  question  of 
the  age  at  which  symptoms  commence.  If  they 
have  their  onset  before  gro^vth  ceases,  gigantism  will 
result.  The  skulls  of  most  of  the  classical  cases  of 
gigantism,  including  Patrick  O'Byrne,  Hunter's 
famous  giant,  and  Patrick  Cotter,  the  Bristol  giant, 
have  enormous  sellae  turcicae  to  accommodate  the 
enlarged  pituitary  gland.  It  is  probable  that  giants 
usually  suffer  from  acromegal}^  as  well.  There  are  two 
authentic  casts  preserved  in  Bristol  of  Patrick  Cotter's 
hand,  one  of  which  is  much  larger  than  the  other ; 
indeed,  it  is  colossal,  measuring  12  inches  from  wrist 
to  finger-tips,  whereas  the  earlier  cast  measures  onh' 
II  inches.  His  shoes,  which  are  also  preserved,  are 
15  inches  long.  It  is  therefore  clear  that  although 
he  was  7  ft.  10  in.  high,  his  hands  and  feet  were  large 
out  of  all  proportion,  and  that  the  hand  rapidly 
increased  in  size  between  the  taking  of  the  first 
and  second  casts.  The  lower  jaw  was  enormous, 
and  out  of  all  relation  to  the  rest  of  the  skull.* 
Cushing  gives  some  striking  photographs  of  a  living 


*  E.   Fawcett,  Jour.  Royal  Anthropological  Institute,   1909,   vol- 
xxxix,  p.  196. 


192  THE    PITUITARY    AXD 

giant,    S  ft.   3  in.   high,    showing    enormous   hands 
and  feet. 

Associated  with  the  enlarged  bones  of  the  face, 
hands,  and  feet  seen  in  acromegaly,  there  are  in  some 
cases  other  features  ;  these  are  glycosuria,  amenor- 
rhoea,  impotence,  and,  in  the  young,  failure  of  the 
secondary  sexual  characters.  The  temperature  is 
subnormal.  This  train  of  symptoms  will  recall  the 
effects  of  total  or  partial  removal  of  the  gland  in 
animals. 

Not  only  the  bones,  but  also  the  \iscera,  may  be 
increased  in  size  in  acromegaly  :  the  kidneys,  liver, 
pancreas,  and  even  the  auriculo-ventricular  bundle  of 
the  heart. 

Frohhch  and  others  have  shown  that  there  is 
another  group  of  cases,  totally  distinct  from  acro- 
megaly, but  again  associated  with  tumours  of  the 
pituitary  gland.  These  are  characterized  by  excessive 
fatness,  by  infantile  stature  and  development,  by  a 
childish  type  of  the  genital  organs,  and  by  absence 
of  the  secondary  sexual  characters.  It  may  be  that 
we  shall  yet  find  abnormahties  of  the  pituitary  gland 
in  other  varieties  of  infantihsm  or  of  adiposity. 

Most  cases  of  pituitary  tumour  which  have  been 
diagnosed  during  hfe  have  given  additional  evidence 
of  their  presence  by  involving  the  optic  chiasma  and 
causing  bhndness  of  the  nasal  half  of  each  retina. 
The  skiagram  shows  enlargement  of  the  sella  turcica. 
In  many  cases  there  are  headache,  vomiting,  and 
other  signs  of  intracranial  pressure. 

We  must  now  attempt  to  classify  our  information, 
and  endeavour  to  com.e  to  some  clear  conception  of 


PINEAL    GLANDS  193 

the  functions  of  the  pituitary  gland,  and  the  causa- 
tion of  these  various  types  of  disease. 

A  year  or  two  ago  it  was  the  prevalent  opinion 
that  the  anterior  and  posterior  lobes  must  be  con- 
sidered to  be  entirely  unconnected  glands,  having  a 
different  development,  histology,  and  function.  The 
posterior  lobe  was  connected  with  the  production  of 
an  internal  secretion,  probably  in  the  colloid  fur- 
nished by  the  pars  intermedia,  which  was  poured 
into  the  ventricular  system  of  the  brain,  and  extracts 
of  this  lobe  raised  the  blood-pressure.  There  is  some 
evidence  that  in  acromegaly  the  anterior  lobe  is 
specially  at  fault  ;  it  may  be  disproportionately 
enlarged,  and  may  show  a  superabundance  of  secre- 
tion granules. 

Now,  however,  there  is  a  tendency  to  unify  the 
functions  of  the  hypophysis  and  to  regard  it  as  one 
gland,  although  the  distribution  of  the  colloid  is 
unequal  in  the  various  parts. 

Whether  the  gland  is  necessary  to  Hfe  is  unsettled. 

The  diseases  fall  into  two  groups  :  those  in  which 
the  internal  secretion  is  excessive  (hyperpituitism), 
and  those  in  which  it  is  diminished  or  absent  (hypo- 
pituitism). 

Hyperpituitism  is  characterized  by  signs  of  acrome- 
galy in  adults,  or  gigantism  if  it  begins  before  growth 
has  ceased.  The  gland  is  usually  enlarged,  showing 
microscopically  a  simple  overgrowth.  There  may 
be  glycosuria.  The  cases  run  a  chronic  course  for 
years  unless  symptoms  of  cerebral  compression 
come  on. 

Hypopituitism  produces  the  FrohHch  type,  with 

13 


194  THE    PITUITARY    AND 

atrophy  of  the  genitals,  infantiUsm,  and  excessive 
fatness.  There  is  often  a  drowsy  mental  state  ; 
indeed,  one  is  tempted  to  believe  that  that  very 
accurate  observer,  Charles  Dickens,  must  have  had 
such  a  case  in  mind  when  he  invented  the  immor- 
tal Fat  Boy  in  Pickudck.  All  these  symptoms  can 
be  mimicked  by  partial  excisions  of  the  pituitary 
gland  in  animals.  Cushing's  results  as  to  which  lobe 
is  at  fault  are  discordant.  Probably,  as  Blair  Bell 
suggests,  it  is  the  whole  gland  that  is  at  fault. 

It  is  true  that  cases  of  acromegaly  may  eventually 
develop  impotence,  sterihty,  and  amenorrhoea  ;  this 
is  explained  as  hypopituitism  succeeding  an  excess. 
The  same  sequence  is  seen  in  diseases  of  the  thyroid 
gland. 

A  very  valuable  measure  of  the  function  of  the 
pituitary  gland  may  be  obtained  by  observations  on 
the  power  of  warehousing  sugar.  If  the  internal 
secretion  is  deficient,  huge  quantities  of  glucose  will 
not  cause  gtycosuria.  This  is  the  cause  of  the  adipo- 
sity. Hypopituitism  is  usually  due  to  maUgnant 
growths  encroaching  on  the  gland,  and  is  frequently 
followed  by  death. 

We  are  now  in  possession  of  some  indications  for 
treatment.  For  acromegaly  and  gigantism  little 
can  be  done.  Pituitary  feeding  does  more  harm 
than  good.  If  there  are  symptoms  of  cerebral 
compression  or  gradually  increasing  bUndness  from 
involvement  of  the  optic  chiasma,  an  operation 
may  be  performed  to  relieve  pressure  and  remove 
part  of  the  gland.  Scores  of  cases  have  now  been 
treated  in  this  way  (Gushing   reports  43  operated 


PINEAL    GLANDS  195 

on  by  himself),  and  the  mortahty  is  not  high.  Several 
observers  record  a  definite  shrinkage  of  the  bones 
afterwards. 

THE    USES    OF    PITUITARY     EXTRACT. 

Patients  suffering  from  the  Frohlich  type  may  be 
treated  by  pituitary  feeding,  the  whole  gland  of 
cattle  being  used.  The  dose  is  about  12  grains  a  day, 
but  Gushing  sometimes  uses  as  much  as  100  grains 
three  times  daily.  This  may  be  worked  out  by  its 
influence  on  the  sugar  tolerance.  Remarkable 
results  have  been  obtained  in  a  few  cases.  If  mouth- 
feeding  is  not  successful,  a  dose  of  whole-gland 
extract  may  be  given  hypodermically  every  twenty- 
four  hours  ;  this  has  proved  very  effectual  some- 
times. If  there  are  signs  of  intracranial  pressure  a 
decompression  operation  is  indicated. 

The  hope  that  pituitary  feeding  would  prove  to  be 
a  remedy  for  increasing  the  stature  of  small  children 
is  not  likely  to  be  realized  in  \'iew  of  the  fact  that 
Schafer  has  failed  to  verify  his  earlier  observations 
on  young  rats. 

Feeding  with  the  whole  gland  is  also  advised  for 
certain  cases  of  amenorrhoea  attributed  to  hypo- 
pituitism.  Unfortunately  it  is  apt  to  cause  severe 
headache. 

On  the  other  hand,  there  is  said  to  be  a  t^-pe  of 
headache  which  is  due  to  disorders  of  the  pituitary 
and  is  often  cured  by  administering  the  whole  gland. 
This  headache  is  frontal,  deep  behind  the  eyes, 
gives  rise  to  great  prostration,  and  there  may  be 
vomiting.  It  is  commoner  in  women  than  men, 
and    may   coincide    with    menstruation.     The    pain 


196  THE    PITUITARY    AND 

lasts  half  an  hour  to  two  days.  There  may  be  a 
craving  for  sweets.  There  may  be  coarse  hair  with 
male  distribution  in  the  female  (Pardee). 

Pituitary  extract,  containing  the  principle  found 
in  the  posterior  lobe  which  acts  on  unstriped  muscle, 
is  now  an  ordinary  article  of  commerce  for  many 
therapeutic  purposes.     It  is  a  favourite  remedy  for 
surgical  and  toxaemic  shock,  and  many  observers  are 
con\'inced  that  it  does  good  by  raising  the  blood- 
pressure.     For  reasons  discussed  in  the  chapter  on 
surgical  shock,  I  am  not  sure  that  pituitary  extract 
is  really  of  any  value  in   this  condition.     A  very 
valuable  effect  is  that  it  promotes  peristalsis  even 
when  purgatives  fail  or  are  vomited,  as  in  cases  of 
intestinal  paralysis   after  abdominal  operations.     A 
third  indication  is  to  increase  labour  pains  ;    some- 
times in  cases  of  weak   pains  the  child  is  expelled 
very  rapidly  after  an  injection.     It  must  not  be  used 
in  obstructed  labour,   or  the  uterus   may  rupture. 
It  is  also  given — is  invaluable  according  to  some — 
in    daily    intramuscular    doses    for    menorrhagia    of 
puberty  or  the  menopause.     It  is  a  powerful  diuretic. 
As  a  galactagogue  its  success  so  far  has  been  doubtful. 
Pituitan."  extract  must  not  be  given  frequently  at 
short  intervals,  or  its  effect  may  be  reversed. 

The  dried  extract  of  posterior  lobe  may  be  given 
orally  in  5 -grain  doses,  combined  with  calcium 
lactate,  for  micnopausal  flushings,  and  with  great 
benefit  {Blair  BeU). 

The  dose  of  the  20  per  cent  extract  used  for 
intramuscular  injection  is  i  to  2  c.c.  for  shock  or 
intestinal  paralysis,  and  0*5  c.c.  for  uterine  inertia. 


PINEAL    GLANDS  197 

THE     PINEAL     GLAND. 

It  has  been  customary  to  look  upon  the  pineal 
gland  as  a  developmental  relic.  The  functionless 
unpaired  eye  of  Hatteria,  which  appears  to  have  been 
present,  possibly  in  functional  form,  in  some  fossil 
reptiles,  is  supposed  to  be  the  substance  of  which  the 
pineal  gland  is  the  useless  shadow.  It  would  be 
trul}^  extraordinary  if  we  had  to  believe  that  a  super- 
fluous relic  had  been  handed  down  from  the  beginning 
of  the  Triassic  period,  throughout  the  whole  family 
of  the  Mammalia,  and  still  persisted  in  man. 

Some  evidence  has  lately  come  to  light  which 
would  lead  us  to  add  the  pineal  to  the  list  of  glands 
with  an  internal  secretion.  It  is  true  that  excision, 
feeding,  and  injection  of  extracts  throw  no  Ught  on 
the  problem  ;  but  histology  shows  that  it  contains 
in  children  glandular  cells,  which  more  or  less  atrophy 
in  adults.  Tumour  of  the  pineal  gland,  in  about  a 
dozen  recorded  cases,  has  been  associated  with  a 
remarkable  precocity,  including  increased  stature, 
premature  development  of  the  genital  organs,  growth 
of  hair,  and,  in  a  few  instances,  an  extraordinary 
mental  vigour.  One  boy,  at  the  age  of  five,  dis- 
coursed learnedly  concerning  the  immortality  of  the 
soul ! 

REFERENCES. 

C'JSHiNG. — The  Pituitary  Gland  and  its  Disorders,  191 1. 

BiEDL. — The  Internal  Secretory  Organs,  1913. 

KiDD. — Med.  Chron.,   1912,  vol.  xxiv,  p.  15^. 

Blair  Bell. — The  Pituitary,  igig. 

Pardee. — Arch.  Int.  Med.,   1919,  xxiii,  p.  174. 


198 


CHAPTER    X, 
OXALURIA. 

IT  has  been  found  very  difficult  to  obtain  reliable 
estimates  of  oxalates  in  the  urine.  The  method 
commonlj'  employed,  introduced  by  Dunlop,  is  open 
to  serious  objections  from  the  chemical  standpoint. 
Working  \vith  O.  C.  M.  Davis,  the  writer  has  used  a 
new  and,  theoretically,  more  reliable  method,  but 
it  is  not  claimed  that  the  results  are  more  than 
approximate.  There  is  still,  therefore,  some  differ- 
ence of  opinion  as  to  the  metabolism  of  the  oxalates, 
but  the  following  conclusions  are  becoming  generally 
accepted. 

In  ordinary  circumstances,  the  whole  of  the  oxalate 
in  the  urine  is  derived  from  articles  of  food.  Milk, 
meat,  and  bread  contain  scarcely  any  oxalate  ;  most 
vegetables  contain  it,  and  rhubarb,  strawberries, 
and  sorrel  contain  a  relatively  large  quantity.  I 
have  by  taking  much  rhubarb  induced  an  attack 
of  oxaluria  sufficiently  marked  to  cause  a  good  deal 
of  smarting  pain  in  the  urethra  from  the  sharpness 
of  the  oxalate  crj^stals.  On  a  milk  diet,  oxalates 
disappear  from  the  urine.  This  may  be  demonstrated 
by  adding  methylated  spirit  and  allowing  to  stand, 
when  any  oxalate  present  in  solution  is  precipitated 
in  characteristic  octahedra.  On  a  milk  diet,  no  such 
crystals  will  be  obtained. 


OXALURIA  199 

None  of  the  ordinary  derangements  of  metabolism 
causes  the  appearance  of  oxalates  in  the  urine  if 
they  are  withheld  from  the  food.  Thus  there  is  no 
oxaluria  in  fever,  in  leukaemia  (illustrating  the 
katabolism  of  nucleoproteins),  or  in  diabetes.  In  a 
case  of  oxalic  acid  poisoning  under  my  care,  the 
excretion  was  enormous,  and  there  was  a  heavy 
deposit  of  calcium  oxalate  crystals. 

It  is  not,  however,  correct  to  say  that  oxaluria 
never  occurs  on  an  oxalate-free  diet,  though  such  a 
condition  is  rare.  As  is  well  known,  the  usual 
products  of  bacterial  fermentation  of  carbohydrates 
in  the  bowel  are  various  gases  (CH,,  CO.J,  lactic, 
acetic,  and  butyric  acids,  and  alcohol.  Miss  Helen 
Baldwin  has  pointed  out  that  in  certain  abnormal 
circumstances  oxalic  acid  also  may  be  formed  in  this 
way.  Copious  feeding  on  sugar  will  ruin  a  dog's 
digestion,  and  then  oxalates  may  appear  in  the  urine 
even  on  an  oxalate-free  diet.  Occasionally  she  has 
met  with  such  cases  in  man.  I  have  not  chanced  to 
observ'e  such  a  case  personally,  and  believe  that  they 
are  not  common. 

Fermentation  of  carbohydrates  in  the  stomach  and 
intestines  to  an  excessive  degree  is  common  enough, 
but  it  is  only  rarely  that  there  is  any  formation  of 
oxalates.  I  have  never  been  able  to  obtain  the 
crystals  either  from  the  gastric  contents  or  from  the 
urine  of  patients  with  obstruction  of  the  pylorus 
and  gastric  dilatation,  on  an  oxalate-free  diet. 

When  ammoniacal  fermentation  of  urine  takes 
place,  as  on  standing,  any  oxalate  crystals  present 
are  rapidly  dissolved  and  disappear. 


200  OXALURIA 

The  oxalate  calculus  is  by  far  the  most  important 
variety  occurring  in  the  kidney.  B.  Moore  has 
shown  that  a  pure  uric  acid  stone  is  found  only  in  the 
bladder,  and  that  all  renal  calculi  are  composed  for 
the  most  part  of  calcium  oxalate.  Tliis  is  fortunate 
for  the  x-Ta.y  diagnosis  of  the  condition,  and  as  it  is 
comparatively  easy  to  control  the  oxalate  excretion, 
it  makes  it  possible  for  us  to  advise  the  patient  how 
to  avoid  a  relapse  after  operation.  To  draw  the 
practical  lessons  from  our  study,  it  is  evident  that 
any  patient  suffering  from  oxaluria  should  abjure 
the  use  of  green  vegetables,  and  fruits  should  be 
taken  sparingly.  If  he  is  obeying  directions,  a  fresh 
specimen  of  his  urine,  mixed  with  an  equal  amount 
of  spirit  and  allowed  to  stand,  will  deposit  only  a 
few  small  crystals  of  oxalate,  and  a  specimen  without 
the  addition  of  spirit  will  show  no  crystals  even  on 
centrifugaUzing.  Occasionally,  however,  one  may 
find  a  case  in  which  oxaluria  persists  even  on  a  milk 
diet.  We  must  then  restrict  the  sugars  and  starches 
of  the  diet,  and  give  remedies  calculated  to  diminish 
fermentation  in  the  stomach  and  intestines. 

If  patients  object  to  dietetic  restrictions,  potassium 
citrate  will  often  reUeve,  both  by  acting  as  a  diuretic, 
and  by  making  the  urine  alkaline,  thus  dissolving 
the  crystals. 

REFERENCE. 
A.      Rendle      Short. — Von     Noorden's      Metabolism     and 
Practical  illedicine,  vol.  i,  p.  148. 


201 


CHAPTER    XI. 

IMMEDIATE    AND    REMOTE     POISONING 
BY     CHLOROFORM. 

SUDDEN  DEATH  UNDER  CHLOROFORM THE  FATAL  ADRENALIN- 
CHLOROFORM        COMBINATION DELAYED        CHLOROFORM 

POISONING. 

ENTHUSIASTIC  advocates  of  chloroform  as  the 
ideal  anaesthetic  (usually  hailing  from  the 
north)  used  to  say,  "  Chloroform  kills  your  patient 
to-day,  and  ether  kills  him  to-morrow".  They 
referred  of  course  to  the  pulmonary  complications 
which  used  to  follow  the  use  of  the  latter  drug  in  the 
days  when  it  was  given  by  a  Clover's  inhaler  through- 
out the  operation,  instead  of  by  the  open  method. 
We  are  now  finding  out  that  chloroform  too  may  not 
claim  its  victims  until  to-morrow. 

Chloroform  may  cause  a  fataUty  in  three  distinct 
ways  :  first,  by  sudden  arrest  of  the  heart  ;  secondly, 
by  poisoning  the  heart  and  \'ital  centres  in  the 
medulla  of  the  brain  ;  and  thirdly,  by  inducing  acute 
fatty  degeneration  of  the  viscera,  and  acidosis.  We 
shall  here  only  consider  the  first  and  third. 

SUDDEN  ARREST  OF  THE  HEART. 

Some  of  the  most  tragic  calamities  of  surgical 
practice  are  due  to  sudden  death  from  chloroform, 
and  few  and  happy  are  the  surgeons  who  have  never 
seen  it.     Here  we  must  place  those  cases  where  the 


202  IMMEDIATE    AND    REMOTE 

patient  is  far  from  under,  perhaps  struggling  and 
shouting,  and  then  without  warning  draws  a  few 
deep  breaths  and  dies.  Here  also,  those  who  seem 
to  be  under,  but  whose  heart  and  respiration  cease  on 
being  hfted  into  position  for  the  surgeon.  Here, 
again,  those  who  have  been  given  a  mere  whiff  of 
the  anaesthetic  for  a  trifling  operation,  and  whose  hfe 
ebbs  away  at  the  bare  touch  of  the  knife. 

Until  recently,  it  was  supposed  that  these  fatahties 
were  due  to  sudden  reflex  stoppage  of  the  heart  by 
way  of  the  vagus,  and  that  view  was  given  in  the 
first  and  second  editions  of  this  book.  Very  im- 
portant research  work  by  Goodman  Levy  appears 
to  demonstrate  that  the  chloroform  acts  directly 
on  the  ventricular  muscle,  and  causes  it  to  fibril- 
late,  that  is,  to  enter  into  flickering  irregular 
contraction  of  individual  fibres,  instead  of  per- 
forming its  proper  rhythmical  systoles.  Working 
with  cats,  Levy  was  able  repeatedly  to  observe 
fatal  ventricular  fibrillation,  usually  heralded  by 
cardiac  irregularity,  and  always  when  the  chloro- 
form anaesthesia  was  fight,  not  deep.  Stimulation 
of  sensory  nerves  under  a  fight  anaesthesia  frequently 
caused  death  in  this  way  ;  in  other  cases,  the  animal 
recovered.  The  effect  was  just  the  same  if  both 
vagi  were  previously  cut.  Levy  found  great  diffi- 
culty in  discovering  exactly  by  what  means  the 
sensory  stimulus  affected  the  heart.  The  connection 
is  probably  complex.  If  the  chloroform  is  given  in  a 
perfectly  continuous  manner  without  intermissions, 
sudden  death — in  cats  at  any  rate — can  be  avoided. 
Struggling,  both  in  man  and  animals,  is  dangerous. 


POISONING     BY    CHLOROFORM        203 

An  apology  must  be  made  for  saying  again  what  we 
all  know,  yet  never  can  know  too  well.  It  is  courting 
disaster  to  hurr^'  the  patient  under.  We  must  feel 
the  pulse  all  the  time,  as  well  as  watch  the  pupil  and 
the  respirations.  '  Whiffs  '  are  far  more  dangerous 
than  proper  anaesthesia.  No  lifting,  or  cutting,  or 
painful  pressure  is  permissible  until  the  patient  is 
properly  under.  There  is  no  danger  of  an  overdose 
during  quiet  breathing  if  the  mask  is  kept  half  an 
inch  away  from  the  face.  If  Levy's  results  are  to  be 
accepted,  the  mask  must  not  be  entirely  withdrawn 
if  struggling  occurs,  but  every  effort  made  to  keep 
the  administration  constant. 

W'hat  is  to  be  done  if  the  calamity  is  not  success- 
fully averted,  and  the  heart  and  breathing  cease  ? 
The  books  advise  a  dozen  expedients.  A  moment's 
consideration  of  physiological  principles  will  lead  us 
to  put  most  of  them  aside.  How  can  amyl  nitrite, 
which  is  simply  a  vasodilator,  possibly  help  a  heart 
that  is  fibrillating  ?  Strychnine  and  brandy  are 
perfectly  futile.  It  is  no  use  gi\'ing  oxygen  to  a 
patient  who  is  not  breathing.  '  Galvanization  of  the 
phrenics  '  is  equally  likely  to  galvanize  the  vagus. 

There  are  just  four  measures  which  matter.  The 
first  is  to  have  the  head  low,  so  as  to  keep  the  \dtal 
centres  aUve.  The  second  is,  of  course,  artificial 
respiration,  which  fills  the  auricles  with  blood  as 
well  as  the  lungs  with  air,  averts  death  from  asphyxia, 
and  so  gives  the  heart  time  to  recover  if  it  can. 
The  third  is  to  stimulate  the  heart  to  contract  again 
by  manual  compression,  if  possible  through  the 
diaphragm.     The  fourth  is  to  administer  as  quickly 


204  IMMEDIATE    AND    REMOTE 

as  possible  atropine,  which  must  be  injected  right 
into  the  heart  by  a  long  hypodermic  needle.*  Its 
value  in  overcoming  chloroform  inhibition  has 
been  abundantly  proved  by  Dixon  and  others  in 
dogs,  and  though  its  use  in  such  cases  in  man  is 
but  recent,  successes  are  already  recorded.  That 
there  have  been  failures  is  admitted,  but  there  is 
good  reason  to  hope  for  recovery  with  immediate 
injection  into  the  heart  .itself.  The  most  dramatic 
recovery  I  ever  witnessed,  in  a  patient  who  seemed 
already  dead  and  in  whom  all  other  means  had 
failed,  was  brought  about  in  this  way.  There  is 
ground  for  hoping,  also,  that  a  preliminarv'  injection 
of  scopolamine,  now  becoming  popular  for  employ- 
ment before  the  administration  of  a  general  anaes- 
thetic, may  help  to  eliminate  these  terribly  sad 
occurrences. 

Several  patients  apparently  passed  beyond  the 
shadowy  Rubicon  which  separates  the  living  from 
the  dead  have  been  brought  back  to  Hfe  by  rapidly 
opening  the  upper  abdomen  and  rhythmically 
squeezing  the  heart  against  the  chest  wall  through 
the  diaphragm. 

THE     FATAL     ADRENALIN-CHLOROFORM 
COMBINATION. 

In  Bristol,  it  has  been  well  recognized  for  ten 
or  twelve  years  that  the  combination  of  chloroform 
anaesthesia    with    injections    of    adrenalin,    as    for 


*  Acropiae  solutions  are  apt  to  grow  a  mould  which  is  very 
poisonous.  If  such  a  growth  is  observed,  the  solution  must  not 
be  used. 


POISONING    BY    CHLOROFORM        205 

instance  into  the  mucous  membrane  of  the  nose  to- 
check  haemorrhage  in  a  nose  operation,  is  a  pecuharly 
deadly  association  of  remedies.  There  have  been 
several  fatalities,  and  a  number  of  narrow  escapes. 
Levy  has  done  most  valuable  service  in  working  out 
the  subject  upon  animals,  and  in  demonstrating 
that  adrenalin  has  a  peculiar  power  in  bringing  on 
the  ventricular  fibrillation  which  is  the  particular 
danger  of  a  light  chloroform  anaesthesia.  A  number 
of  deaths  have  now  been  recorded  from  this  cause 
in  medical  literature.  The  adrenalin-ether  combina- 
tion appears  to  be  safe. 

DELAYED     CHLOROFORM    POISONING. 

The  third  danger  from  chloroform  anaesthesia  is 
subtle  and  unexpected,  and  we  do  not  know  how  to 
treat  its  symptoms. 

It  is  well  known  that  the  katabolism  of  fats  ia 
the  body  may  follow  an  abnormal  sequence  when 
the  amount  of  glucose  supphed  to  the  tissues  by 
the  blood  is  deficient.  In  these  circumstances,, 
/j-oxybutyric  acid,  diacetic  (or  aceto-acetic)  acid,  and 
acetone  are  produced,  and  the  patient  is  poisoned 
by  the  acids,  while  the  acetone  imparts  a  sweet 
odour  to  the  breath  and  urine.  Starved  patients- 
and  diabetics  are  particularly  liable  to  this  condition 
of  'acidosis'  or  '  acetonaemia',  as  it  is  variously 
called.  Fat  children  and  sufferers  from  peritonitis 
are  frequently  the  subjects  of  acidosis  after  opera- 
tions in  which  chloroform  has  been  used,  and  there  is 
greater  danger  if  there  has  been  a  long  interval 
between  the  last  feed  and  the  anaesthetic.     A  pro- 


206  IMMEDIATE    AND    REMOTE 

longed  administration  is  more  dangerous  than  a 
brief  one.  The  train  of  symptoms  is  referred  to 
as  delaj^ed  chloroform  poisoning.  A  hospital  of 
200  beds  may  perhaps  furnish  one  or  two  such 
cases  annually,  if  chloroform  is  used  frequently  as 
the  anaesthetic  of  choice.  The  signs  are  incessant 
vomiting,  drowsiness  or  unconsciousness,  and  a 
sweet  acetone  odour  in  the  breath.  Acetone  and 
aceto-acetic  acid  are  present  in  considerable  amount 
in  the  urine.  A  trace  may  often  be  found  after 
any  anaesthetic.  Death  follows  within  a  few 
days.  At  the  post-mortem  examination  the  liver, 
kidneys,  and  other  organs  show  signs  of  acute 
fatty  degeneration.  Whether  this  is  the  cause 
or  the  consequence  of  the  acidosis  may  be  in 
doubt,  but  the  vomiting  and  drowsiness  are  almost 
certainly  due  to  the  effect  of  the  acid  intoxication 
on  the  brain.  Most  surgeons  who  are  aware  of  the 
condition  can  recall  sad  cases  where  an  operation 
promised  well,  but  this  fatal  comphcation  stepped 
in  and  banished  all  hope  of  a  favourable  issue. 
Recently  it  has  been  found  possible  to  imitate  the 
condition  in  experimental  animals.  To  draw  the 
practical  lesson,  we  can  at  present  hope  only  to 
prevent,  not  to  cure.  Every  patient  to  whom  it 
may  be  necessary  to  administer  chloroform  should 
be  guarded  as  far  as  possible  against  this  comph- 
cation. The  urine  should  be  tested  with  ferric 
chloride.  A  prolonged  starvation  should  be  avoided. 
Glucose  and  alkalies  have  been  advocated  as  remedies 
likely  to  prevent  trouble,  and  the  former  appears 
to  be  the  better.     If  possible,  ether  should  be  given 


POISONING     BY     CHLOROFORM        207 

to  patients  who  have  been  starved,  to  fat  children, 
and  especially  to  patients  whose  urine  strikes  a  red 
colour  with  ferric  chloride.  Diabetics  require  special 
care.  If  prolonged  v^omiting  follows  recovery  from 
the  anaesthetic,  the  poison  should  be  diluted  by  a 
large  injection  of  saline  into  the  rectum,  which  often 
works  wonders.  If  acetone  can  be  smelt  in  the 
breath,  glucose  or  alkalies,  or  both,  should  be  intro- 
duced into  the  blood  by  transfusion,  but  success  is 
not  very  probable,  as  these  remedies  cannot  restore 
the  fatty  liver  and  other  viscera  to  normal. 

Whether  the  acidosis  is  the  cause  of  the  vomiting, 
or  whether  the  starvation  consequent  on  the  vomiting 
causes  the  acidosis,  is  not  yet  certain,  but  we  may 
safely  attribute  the  drowsiness  to  the  acids  in  the 
blood,  and  they  probably  share  in  bringing  about 
the  fatal  termination. 

REFERENCES. 

Goodman  Levy. — Brit.  Med.  Joiir.,  19 12,  ii,  p.  62 7. 
Goodman  Levy. — Heart,  19 13,  June,  p.  319. 


208 


CHAPTER    XI I. 

THE     FUNCTIONS     OF     THE      SPINAL 
CORD     AND     PERIPHERAL     NERVES. 

THE    DOUBLE    MOTOR    PATH THE    DOUBLE    SENSORY    PATH 

THE     EXACT     DIAGNOSIS     OF     SPINAL     CORD     INJURIES 

LESIONS  OF  THE  POSTERIOR  NERVE  ROOTS — INJURIES  AND 
REPAIR   OF  PERIPHERAL   NERVES. 

IN  this  chapter,  as  in  so  many  others,  we  shall 
find  that  the  injuries  sustained  by  the  wounded 
in  the  great  war  have  shed  a  light  on  problems  of 
function,  though  the  investigations  we  have  first  to 
describe  savour  more  of  civilian  than  military 
practice. 

THE     DOUBLE     MOTOR     PATH. 

We  had  become  accustomed  to  think  and  speak 
of  a  single  path  for  voluntary  movements,  consisting 
of  an  upper  motor  neurone,  the  pyramidal  Betz  cells 
of  the  precentral  cortex  and  the  pyramidal  tract 
fibres,  and  a  lower  motor  neurone,  the  anterior  horn 
cells  of  the  spinal  cord  (or  motor  nucleus  in  the 
brain  stem)  and  the  medullated  fibres  of  the 
peripheral  nerves.  There  is  now  to  be  considered 
a  good  deal  of  evidence  that  the  motor  path  is 
doubled  throughout. 

It  has  long  been  suspected  that  the  pyramidal 
tracts  could  not  be  the  only  motor  path.  Babies 
can  move  their  limbs  before  the  pyramids  myelinate. 


FUNCTIONS    OF    THE    SPINAL    CORD    209 

After  a  hemiplegic  stroke,  certain  stock  movements 
such  as  standing  and  walking  may  persist,  although 
the  fibres  of  the  pyramidal  tracts  may  be  almost 
entirely  destroyed.  In  animals,  as  is  well  known, 
quite  extensive  lesions  of  these  tracts  or  of  the  motor 
cortex  do  not  produce  lasting  paralysis,  even  in  the 
chimpanzee.  Thromboses  spoiling  the  arm  centre, 
or  the  face  centre,  in  man,  give  rise  to  paralysis, 
but  there  is  often  a  remarkable  degree  of  recovery 
of  function  later.  In  old  hemiplegias,  voluntary 
movement  of  the  sound  side  may  be  accompanied 
by  involuntary  movements  of  the  hemiplegic  limbs. 
Similar  movements  may  be  obtained  in  the  cat  or 
chimpanzee  by  stimulating  the  red  nucleus  area. 
In  the  foetal  cat  the  movements  resemble  those  of 
walking  (Graham  Brown). 

The  phenomena  of  spasticity  point  in  the  same 
direction.  It  is  well  knov/n  that  after  a  hemiplegic 
stroke  due  to  a  lesion  in  the  internal  capsule  there 
is  marked  rigidity  of  the  paralyzed  side.  Also  in 
any  animal  a  transection  of  the  mesencephalon 
brings  on  a  state  of  *  decerebrate  rigidity/  the  limbs 
becoming  as  stiff  as  if  frozen.  A  second  transection 
below  the  fourth  ventricle  abolishes  this  rigidity  ; 
a  hemisection  abolishes  it  on  the  side  divided. 
Division  of  the  posterior  nerve  roots  of  a  limb  sets 
that  limb  free  from  the  rigidity.  Evidently,  there- 
fore, there  is  another  innervation  for  the  muscles 
besides  that  due  to  the  pyramidal  tract,  and  a  re- 
flex arc  responsible  for  producing  the  spasticity. 
The  researches  of  Sherrington,  Thiele,  Weed,  and 
Bergmark  seem  to  indicate  that  the  path  for  the 

14 


210    THE    FUNCTIONS    OF    THE    SPINAL 

reflex  is  as  follows  :  posterior  nerve  root,  tract  of 
Gowers,  cerebellum,  superior  cerebellar  peduncle,  red 
nucleus,  rubrospinal  tract.  Section  of  any  of  these 
tracts  will  abolish  decerebrate  rigidity.  Lesions  of 
the  inferior  cerebellar  peduncle  do  not  influence  the 
spasticity'.  The  pyramidal  and  frontopontic  and 
temporo-occipito-pontic  tracts  inhibit  muscular  tone. 
A  pure  cortical  lesion  frequently  causes  a  flaccid 
paralysis,  whereas  a  lesion  of  the  internal  capsule 
gives  rise  to  spasticity,  because  in  the  latter  case  all 
the  inhibitory  tracts  are  likely  to  be  involved, 
whereas  a  pure  lesion  of  the  precentral  cortex  spares 
the  corticopontic  tracts. 

We  find,  then,  two  motor  paths  in  the  brain-stem 
and  spinal  cord  : — • 

1.  The  pyramidal  tract,  descending  from  the 
cerebral  cortex,  controlling  finer  and  more  skilled 
movements,  inhibiting  muscular  tone. 

2.  The  rubrospinal  tract,  descending  from  the  red 
nucleus  (probably  influenced  by  the  lenticular 
nucleus),  controlhng  stock  elementary  movements, 
and  exaggerating  muscular  tone.  Perhaps  the 
various  anterolateral  descending  tracts  (vestibulo- 
spinal, tectospinal,  and  the  like)  share  in  the 
function. 

But  it  is  not  only  in  the  central  ner\^ous  system 
that  evidence  has  been  found  of  a  double  motor 
path.  Ramsay  Hunt  has  some  interesting  observa- 
tions to  bring  forward  pointing  to  a  double  path  in 
the  motor  nerves.  There  are,  for  instance,  end-plates 
in  striped  muscle  of  non-medullated  as  well  as  of 
medullated  nerve-fibres   (Boeke),    and    Ransom  has 


CORD    AND     PERIPHERAL    NERVES    211 

shown  by  his  silver-pyridine  method  that  the  peri- 
pheral nerves  contain  a  lot  of  non-meduUated  fibres. 
Striped  muscle  itself  contains  two  elements  ;  each 
fibre  consists  of  a  great  number  of  cross-banded 
sarcostyles  packed  in  sarcoplasm,  as  though  a  bundle 
of  cross-striped  pencils  were  put  into  a  cylinder-glass 
containing  treacle.  In  muscles  designed  for  rapid 
action  the  sarcostyles  predominate  ;  in  muscles  where 
long,  slow  contraction  is  needed  there  is  relatively 
more  sarcoplasm.  The  sarcoplasm  (corresponding  to 
the  treacle)  is  itself  contractile.  The  suggestion  is  that 
there  is  an  older,  simpler  mechanism,  consisting  of 
rubrospinal  tract,  fine  and  non-medullated  nerve- 
fibres,  Boeke's  end-plates,  and  sarcoplasm  ;  and  a 
newer  mechanism  capable  of  greater  quickness  and 
higher  control — the  pyramidal  tract,  coarse  medul- 
lated  nerve  fibres,  ordinary  motor  end-plates,  and 
sarcostyles.  In  the  intercostal  nerves,  fine  fibres 
are  in  excess  ;  in  the  brachial  plexus,  coarse  fibres. 

Some  curious  phenomena  in  the  healing  of  nerve 
lend  support  to  the  hypothesis.  Ramsay  Hunt 
describes  cases  in  which  after  suture  there  was  a 
period  during  which  muscular  tone  and  associated 
movements  had  returned,  but  voluntary  power  had 
not  yet  been  recovered  ;  indeed,  in  certain  cases  of 
musculospiral  palsy  it  never  did  recover.  The 
facial  nerve  shows  this  phenomenon  best.  There 
may  be  recovered  tone,  and  even  spasm,  vnth 
restoration  of  such  symmetrical  movements  as 
smiling,  long  before  return  of  voluntary  movement. 
The  finer  and  non-medullated  fibres  have  presumably 
regenerated  before  the  coarser. 


212    THE    FUNCTIONS    OF    THE    SPINAL 

THE     DOUBLE     SENSORY     PATH. 

The  researches  of  Head  and  his  fellow-workers 
have  shown  that  peripheral  sensation  may  be  grouped 
under  three  headings  : — 

1.  Epicritic  sense,  including  localization,  light 
touch,  and  slighter  variations  of  temperature. 

2.  Protopathic  sense,  a  more  elementary  mechanism, 
preserved  in  the  glans  penis,  and  made  evident  after 
certain  nerve-injuries,  recognizing  pain,  and  greater 
variations  of  temperature. 

3.  Deep  sensibility,  appreciating  deep  pressure. 
Probably    there    are    three    different    nerve-fibre 

paths  subserving  these  functions. 

In  the  spinal  cord,  however,  a  new  grouping  takes 
place  ;  heat,  cold,  and  pain  sense  travel  by  one 
route,  and  stereognosis,  tactile  discrimination,  and 
kinaesthetic  sense  (sense  of  weight,  and  sense  of 
position)  by  another. 

An  interesting  investigation  has  just  been  pub- 
lished by  Ransom  throwing  some  light  on  the  way 
in  which  this  re-grouping  occurs.  The  bulk  of  the 
fibres  in  a  spinal  posterior  nerve-root  are  non- 
medullated,  only  shown  by  special  stains  ;  they 
have  the  usual  cell-station  in  the  posterior  root 
ganglion,  and  the  axon  shows  the  T-shaped  bifurca- 
tion. The  centripetal  branch  of  these  non-meduUated 
fibres  enters  the  tract  of  Lissauer,  and  immediately 
plunges  into  the  grey  matter  of  the  posterior  horn. 
There  are  thus  inner  and  outer  divisions  of  the 
entering  posterior  nerve-roots  ;  the  inner  medullated 
fibres  enter  the  columns  of  Burdach,  and  the  outer 
non-medullated    enter    the  gelatinous   substance   of 


CORD    AND    PERIPHERAL    NERVES    213 

Rolando,  Section  of  the  outer  division  abolishes 
the  evidences  of  pain  such  as  strugghng,  the  pressor 
vasomotor  reflex,  and  quicker  breathing,  in  the 
lightly  anaesthetized  animal,  when  the  sensory  nerves 
are  stimulated.  Section  of  the  inner  root  has  no 
such  effect.  It  is  suggested,  therefore,  that  the 
outer  non-medullated  root  is  the  path  for  pain  and 
temperature  sense,  and  that  the  inner  medullated 
root  is  the  path  for  muscular  sense,  stereognosis, 
and  tactile  sense. 

As  already  remarked,  there  is  a  double  sensory 
path  up  the  spinal  cord.  Leaving  out  of  considera- 
tion those  tracts  (the  dorsal  and  ventral  cerebellar, 
etc.)  which  do  not  carry  up  messages  to  the  centres 
for  consciousness,  and  also  leaving  out  of  account 
the  possibility  that  sensory  impulses  may  be  trans- 
mitted up  the  grey  matter  of  the  cord  with  its  short 
endogenous  connecting  fibres,  there  remain  two  main 
ascending  tracts.     These  are  : — 

1.  The  posterior  columns  of  Gcll  and  Burdach, 
whose  axons  are  derived  from  the  entering  posterior 
nerve-roots,  which  run  uncrossed  up  to  the  gracile 
and  cuneate  nuclei  ;    and 

2.  The  spinothalamic  tracts,  arising  in  the  cells  of 
the  posterior  horn,  mostly  of  the  opposite  side, 
running  up  in  the  tract  of  Gowers,  joining  the  mesial 
fillet  in  the  brain-stem,  and  ending  in  the  optic 
thalamus. 

The  messages  conveyed  by  the  columns  of  Goll 
and  Burdach  are  also  carried  on  to  the  optic 
thalamus,  by  way  of  the  mesial  fillet. 

According  to  our  present  interpretation,  which  has 


214    THE    FUNCTIONS    OF    THE    SPINAL 

to  be  based  almost  entirely  on  human  evidence 
because  animals  cannot  explain  their  feelings,  pain 
and  temperature  sense  are  conveyed  by  the  spino- 
thalamic tract,  whereas  muscular  sense,  joint  sense, 
and  tactile  discrimination — by  which  we  distinguish 
whether  two  compass  points  are  double  or  single — ^pass 
up  the  posterior  columns  ;  the  sense  (stereognosis)  by 
which  we  recognize  unseen  objects  by  the  feel — 
as  on  putting  a  hand  into  a  pocket  containing  coins, 
keys,  a  penknife,  paper,  etc. — also  travels  by  this 
route. 

Thus  we  find  that  whilst  muscular  sense,  stereo- 
gnosis, and  tactile  discrimination  pass  up  the  cord 
uncrossed,  heat,  cold,  and  pain  senses  cross,  and 
there  is  a  cell-station  in  the  grey  matter.  Pain 
crosses  at  once  ;  temperature  and  tactile  sense 
usually  about  five  segments  above.  Hence  syringo- 
myelia and  other  lesions  of  the  grey  matter  abolish 
temperature  and  pain  sense.  Sherrington  has  shown 
that  the  pain  impulses  are  not  totally  crossed  ;  a  few 
pass  up  on  the  same  side.  Tactile  sense,  apparently, 
can  follow  either  of  these  two  routes. 

The  diseases  which  throw  most  light  on  these 
problems  are  tumours  of  the  spinal  cord,  and 
syringomyelia. 

A  tumour  of  the  spinal  cord  : — 

1.  May  affect  the  nerve-roots,  in  which  case  the 
symptoms  may  be  confined  to  those  roots. 

2.  May  press  on  one  side  of  the  spinal  cord.  In 
this  case  there  is  usually  pain  radiating  along  the 
nerve-roots  involved  at  the  same  time,  which  is 
important  in  the  diagnosis. 


CORD    AND    PERIPHERAL    NERVES    215 

Let  us  take  the  case  of  a  tumour  in  the  left  lower 
cervical  area.     This  will  involve  : — 

(i).  The  emerging  roots  of  the  lower  cervical  nerves 
on  the  left  side,  causing  pain,  dulling  of  sensation, 
and  flaccid  paralysis  with  loss  of  reflexes,  wasting, 
and  reaction  of  degeneration,  in  the  left  arm. 

(ii).  The  pyramidal,  ruhrospinal,  and  vestibulo- 
spinal tracts  on  the  left  side  causing  paralysis  of 
the  left  le,(?.  Inasmuch  as  the  pyramidal  tract  is 
involved,  muscular  tone  will  be  greatly  increased. 
There  will  be,  therefore,  rigidity  of  the  left  leg  and 
exaggerated  reflexes. 

(iii).  The  cerebellar  tracts  and  posterior  columns  of 
the  left  side,  causing  loss  of  muscle  and  joint  sense, 
and  loss  of  tactile  discrimination  and  recognition  of 
objects  on  the  left  side. 

Table  to   Illustrate  the  Effects  of  a  Tumour 
OF  THE  Left  Lower  Cervical  Region. 


Right  Arm. 
Normal. 


Right  Leg. 

Loss  of  sense  of  heat, 
cold,  pain. 


Left  Arm. 

Pain.  Some  anaesthesia. 
Flaccid  paralysis,  loss  of 
reflexes,  wasting. 


Left  Leg. 

Loss  of  muscular  sense, 
joint  sense,  tactile  discri- 
mination and  recognition  of 
objects.  Spastic  paralysis ; 
exaggerated  reflexes. 


(iv).  The  spinothalamic  tract,  by  which  heat,  cold, 
and  pain  travel  up  from  the  right  leg,  will  also  be 
pressed  upon. 


216    THE    FUNCTIONS    OF    THE    SPINAL 

Tactile  sense  may  not  be  lost  in  either  leg,  as  a 
double  path,  the  one  crossed  and  the  other  uncrossed, 
is  open  to  it. 

3.  It  may  arise  in  the  central  grey  matter.  In  this 
case  there  will  be  loss  of  the  heat,  cold,  and  pain 
senses  on  both  sides,  but  tactile  and  muscular  sense 
will  remain.  There  may  be  some  spastic  paralysis 
of  both  legs.  In  the  early  stages  the  diagnosis  from 
syringomyelia  may  be  only  a  matter  of  opinion. 

4.  In  some  cases  it  may  produce  bilateral  spastic 
paralysis  with  involvement  of  the  sphincter  func- 
tions and  with  ansesthesia  wdthout  any  dissociation 
phenomena.  The  diagnosis  from  transverse  myehtis 
or  vascular  lesions  is  then  ver^'  difficult. 

Each  of  the  thirty-one  nerve  roots  issuing  from 
the  spinal  cord  has  a  definite  distribution,  which 
may  be  motor,  sensory,  and  visceral,  and  these  have 
now^  been  ascertained  with  some  accuracy  by  a  com- 
bination of  anatomical,  physiological,  and  clinical 
methods.  As  given  in  the  various  text-books  and 
monographs,  the  information  is  a  good  deal  more 
than  most  of  us  can  carry  conveniently  in  our 
memories.  It  is  hoped  that  the  bare  elements  set 
down  in  the  table  may  be  found  easier  to  remember, 
and  adequate  for  most  purposes.  Xo  two  accounts 
agree  exactly. 

The  main  points  may  be  emphasized  first.  With 
regard  to  the  sensory  distribution,  there  is  a  good 
deal  of  overlap,  especially  in  the  hand,  where  the 
seventh  cer\dcal  supplies  the  radial  half,  the  eighth 
cervical  the  inner  half,  and  the  first  dorsal  the  one 
and  a  half  fingers  to  which  the  ulnar  nerve  may  be 


CORD    AND    PERIPHERAL    NERVES    217 

traced.  The  twelve  dorsal  nerves  supply  the  chest 
and  abdomen  in  bands  like  successive  strips  of 
plaster  stretched  round  the  body  ;  the  nipple  lies 
between  the  fourth  and  five  dorsal,  and  the  umbilicus 
between  the  ninth  and  tenth.  If  we  place  the  open 
hand  on  the  thigh  just  below  and  parallel  to  Poupart's 
ligament,  we  cover  the  first  lumbar  area ;  the  next 
handbrcadth  below  is  the  second  lumbar,  and  the 
next,  including  the  region  of  the  patella,  is  the  third 
himbar.  The  small  sciatic  nerve  area  corresponds  to 
the  second  sacral,  and  the  internal  saphenous  nerve 
area  to  the  fourth  lumbar  segment. 

With  regard  to  motor  distribution,  the  fifth  cervical 
supplies  the  deltoid  +  biceps  -r-  supinator  longus  group, 
as  weU  as  the  dorsal  scapular  muscles  and  rhomboids. 
In  infantile  palsy  and  other  anterior  horn  or  nerve- 
root  affections,  these  muscles  may  be  found  paralyzed 
and  atrophied  in  company.  On  the  other  hand,  a 
fracture  of  the  spine  irritating  this  segment  brings 
about  a  characteristic  position  of  the  arms  |  .  The 
first  dorsal  gives  off  sympathetic  branches  dilating 
the  pupil. 

The  anatomy  of  the  lumbosacral  plexus  makes  it 
easy  to  remember  that  the  quadriceps  and  adductors 
must  be  supplied  from  the  lumbar  ner\'es,  whereas  the 
hamstrings  and  crural  muscles  are  innerv^ated  from  the 
sciatic  roots.  There  is  a  general  tendency  for  flexors 
to  derive  their  nerve-supply  from  a  level  slightly 
below  that  for  the  extensors.  It  is  easy  to  see 
why  this  should  be  the  case  if  we  glance  at  a 
quadruped,  where  the  flexors  are  posterior  to  the 
extensors. 


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220    THE    FU>XTIONS    OF    THE    SPINAL 

Flaccid  paralysis  and  anaesthesia  of  the  lower  limbs, 
with  sphincter  trouble,  may  be  due  to  a  tumour 
growing  either  in  the  cauda  equina  or  in  the  conus 
medullaris  of  the  cord  itself.  The  diagnosis  is  often 
difficult,  but  tumours  of  the  cauda  are  usually 
characterized  by  a  slower  course,  asymmetry,  very 
violent  pain,  and  Lasagne's  sign — pain  on  flexing  the 
thigh  and  thus  pulling  on  the  nerve-roots.  Operative 
interference  gives  better  results  in  these  cases  than 
in  those  where  the  cord  itself  is  affected. 

In  a  few  cases  recently  recorded,  where  section  of 
posterior  nerve-roots  had  failed  to  relieve  pain,  a 
surgeon  has  divided  the  pain-path  in  the  antero- 
lateral region  of  the  cord.  To  give  success,  this 
should  be  done  on  both  sides,  although  by  far  the 
greater  number  of  pain-fibres  are  crossed.  Sherrington 
worked  out  the  path  by  dividing  the  mesencephalon 
in  dogs,  after  which  injury  they  still  turn  and  try  to 
bite  and  growl  if  a  foot  is  hurt,  although  they  cannot, 
of  course,  psychically  feel  it.  If  then  the  spinal 
cord  is  hemisected  on  the  right  side,  painful 
stimuli  applied  to  the  right  foot  produce  much 
livelier  snapping  and  growling  than  the  same  on 
the  left  side. 

Souttar  has  recorded  a  case  in  which  he  divided 
the  right  anterolateral  region  of  the  cord  in  the 
upper  dorsal  region  for  unilateral  left-sided  gastric 
crises  of  tabes.  The  pain  was  completely  abolished, 
but  not  the  vomiting.  No  paralysis  resulted.  Pain 
sense  in  the  left  leg  was  abolished  ;  tactile,  muscular, 
and  joint  sense  remained.  Strange  to  say,  tempera- 
ture   sense    also    remained    unimpaired.     Although 


CORD    AND     PERIPHERAL    NERVES    221 

pain  sense  crosses  almost  at  the  level  at  which  it 
enters,  and  temperature  sense  several  segments 
further  up,  one  would  have  expected  all  the  messages 
entering  in  the  lumbospinal  region  to  have  got 
across  before  reaching  the  upper  dorsal  level.  Great 
heat  was  interpreted  as  pain. 

THE    EXACT    DIAGNOSIS    OF    INJURIES    OF    THE 
SPINAL    CORD. 

The  following  lesions  of  the  cord  may  be  responsible 
for  symptoms  of  paralysis  or  anaesthesia  after  an 
injury  to  the  back. 

1.  Simple  concussion,  the  injuries  being  micro- 
scopical or  functional  only,  and  the  paralysis  transient. 

2.  Complete  division  of  all  the  nervous  elements. 

3.  Pressure  on  the  cord,  due  to  bone,  callus,  or  a 
foreign  body,  not  causing  a  total  transection. 

4.  Haemorrhage  into  the  spinal  membranes. 

5.  Haemorrhage  into  the  cord  itself. 

6.  Later  compHcations  such  as  myelitis,  traumatic 
neurasthenia,  etc. 

This  is  not  the  place  to  consider  all  these  in  their 
surgical  bearing.  We  want  to  look  at  them  in 
relation  to  the  physiology  of  the  spinal  cord. 

Both  in  man  and  in  animals,  particularly  monkeys, 
a  transverse  injury  to  the  cord  leads  to  the  pheno- 
menon known  as  spinal  shock.  All  the  reflex 
functions  are  severely  depressed,  and  there  is 
transient  paralysis  and  anaesthesia.  Sherrington  has 
showTi  in  animals  that  a  transection,  e.g.,  in  the 
upper  dorsal  region,  causes  spinal  shock  only  distal 
to  the  lesion  ;   the  cervical  cord  is  normal.     If  after- 


222    THE    FUNCTIONS    OF    THE    SPINAL 

recovery  has  occurred  a  second  section  is  made  in 
the  mid-dorsal  region,  no  spinal  shock  is  produced. 
Evidently  it  was  due  to  the  withdrawal  of  impulses 
running  downwards  from  the  brain-stem,  probably 
from  the  region  of  Deiters'  nucleus,  because  tran- 
section of  the  upper  pons  or  mesencephalon  does  not 
cause  spinal  shock. 

Considerable  difficulty  may  be  experienced  for  a 
day  or  two  in  deciding  whether  a  patient  is  suffering 
from  a  complete  division  of  the  cord  due  to  the  nip 
at  the  moment  of  fracturing  the  spine,  or  whether 
the  symptoms  are  due  merely  to  concussion.  In 
the  latter  case  a  few  da^^s'  rest  will  effect  a  cure. 
Sometimes  one  can  get  a  hint  earlier.  If  the  distri- 
bution of  the  paralysis  does  not  correspond  to 
the  distribution  of  the  anaesthesia,  and  if  the  sym- 
ptoms are  asymmetrical,  it  is  probable  that  they  are 
due  partly  at  least  to  concussion. 

Spinal  shock  resulting  from  a  complete  transection 
in  animals  is  very  transient.  In  frogs  it  lasts  a  few 
minutes,  in  cats  and  dogs  a  day  or  less,  in  monkeys 
not  much  more.  In  a  series  of  wounded  men  whose 
cords  had  been  divided  by  gunshot  injury,  if  the 
patient  was  carefully  looked  after,  shock  passed  oft 
in  one  to  three  weeks.  In  such  cases  there  are  three 
stages  distinguishable  : — 

1.  Period  of  spinal  shock,  with  absent  reflexes  and 
paralysis  of  the  bladder. 

2.  Period  of  recovery ;  reflexes  returned,  and 
bladder  empties  itself  automatically  when  full. 

3.  Period  of  terminal  failure,  when  the  isolated 
segment    of    the    spinal    cord    suffers,   from    toxic 


CORD     AND     PERIPHERAL    NERVES     223 

degeneration  or  myelitis,  and  reflexes  again  fail,  with 
paralysis  of  bladder,  great  wasting  of  the  legs  and 
reaction  of  degeneration,  and  trophic  changes. 

Sometimes  the  period  of  recovery  is  absent, 
especially  if  the  patient  becomes  infected  ;  this  used 
to  be  described  as  the  normal  in  man  when  the  cord 
is  completely  divided,  but  it  is  now  abundantly 
proved  that  there  may  be  well-marked  recovery  of 
reflexes  and  spasticity  even  with  an  absolute  tran- 
section. 

It  is  frequently  impossible  from  the  symptoms  and 
physical  signs  to  decide  whether  the  injur^^  to  the 
cord  is  complete  or  incomplete.  Of  course,  if  any 
sensation  persists,  or  any  true  voluntary  control, 
some  tracts  must  still  be  left. 

Even  in  the  absence  of  any  sensation  or  voluntary 
control  in  the  parts  below  the  injury,  Riddoch  has 
put  us  in  possession  of  a  sign  that  may  sometimes 
be  of  value.  It  used  to  be  taught  that  if  the  legs 
were  rigid  and  showed  reflexes,  the  transection  was 
incomplete.     This  is  not  true. 

The  spasms  that  may  be  reflexly  elicited  in  a  case 
of  complete  transection  are,  however,  always  flexor, 
never  extensor.  If  extensor  reflexes  or  movements 
of  progression  can  be  obtained,  as  by  pricking  the 
thighs  or  drawing  the  prepuce  over  the  erect  penis, 
the  lesion  of  the  cord  is  incomplete. 

The  practical  point  of  course  is  that  with  an 
incomplete  injury  it  is  well  worth  while  to  operate 
to  remove  pressure  ;  if  the  conducting  elements 
are  totally  divided,  operation  is  useless. 

The  flexor  spasms  of  the  thighs  elicited  by  stroking 


224    THE     FUNCTIONS     OF    THE     SPINAL 

the  inner  side  are  often  accompanied  by  reflex 
emptying  of  the  bladder.  This  may  aid  in  keeping 
the  patient  dry,  by  getting  the  urine  evacuated 
regular!}'  without  needing  a  catheter. 

Marked  wasting  of  the  legs  generally  means  a 
complete  transection  and  a  hopeless  prognosis. 

Lesions  of  the  cauda  equina  may  wiseh'  be  explored, 
because  suture  of  the  roots  or  removal  of  pressure 
may  lead  to  regeneration. 

Haemorrhage  into  the  spinal  membranes  produces 
pain  and  spasm  by  involving  the  issuing  nerve-roots. 
In  addition,  there  will  probably  be  some  evidence  of 
pressure  on  the  cord,  producing  spastic  paralysis  and 
some  anaesthesia  below  the  lesion. 

Haemorrhage  into  the  centre  of  the  cord  sometimes 
abolishes  the  pain  and  temperature  senses  while 
tactile  sense  escapes.  There  will  probably  be  spastic 
paraplegia  as  well. 

It  will  not  be  necessary  to  refer  here  to  the  diagnosis 
of  the  later  complications,  such  as  myelitis  and  the 
various  neuroses. 

Unfortunately  the  central  nervous  system  is  so 
highly  specialized  that  it  has  lost  the  power  of 
regeneration  after  injury,  not  only  in  man  (unless  we 
accept  the  evidence  of  the  famous  Stewart-Harte 
case  I)  but  also  in  nearly  all  animals.  The  newt,  it  is 
true,  can  form  a  new  cord  if  its  tail  is  lopped  off,  but 
the  newt  has  marvellous  powers  of  regeneration,  and 
can  even  grow  a  new  lens  if  the  front  of  its  eye  is 
removed  !  Histological  evidence  of  partial  regenera- 
tion has  been  obtained  in  mammals  by  Marinesco 
and  others,  but  not  functional  restoration. 


CORD    AND    PERIPHERAL    NERVES     225 

THE    EFFECTS    OF    DIVISION    OF    THE 
POSTERIOR    NERVE-ROOTS. 

The  effects  may  be  classified  as  follows  : — 

1.  Anaesthesia  of  the  spinal  area  of  skin  supplied. 
The  distribution  of  these  in  the  human  subject  has 
been  worked  out  thoroughly,  and  the  charts  of  Head, 
Sherrington,  and  others  are  well  kno\NTi.  Section  of 
a  single  nerve-root  scarcely  ever  causes  any  complete 
loss  of  sensation. 

2.  Ataxia  of  the  corresponding  limb,  which  may  be 
severe. 

3.  Loss  of  tone,  leading  to  marked  fiaccidit}'  of 
the  corresponding  limb. 

4.  A  variable  degree  of  functional  paral^'sis. 
Owing  to  the  loss  of  sensory  impulses,  the  ataxia, 
and  lack  of  tone,  the  patient,  man  or  animal,  prefers 
not  to  use  the  limb,  although  there  is  not  a  genuine 
paralysis. 

5.  Loss  of  reflexes. 

6.  Trophic  lesions,  such  as  ulcers,  whitlows,  etc. 
It  has  recently  been  shown  by  Eloesser  that  bone 

and  joint  diseases  similar  to  the  Charcot  joints  of 
locomotor  ataxia  can  be  produced  in  cats  by  dividing" 
all  the  posterior  ner\-e-roots  to  a  limb  and  then 
bruising  or  crushing  the  joints.  Similar  treatment 
of  the  joints  on  the  side  \\ith  sensory  nerves  intact 
gave  rise  to  no  such  changes.  Extensive  and 
grotesque  departures  from  the  normal  were  secured 
in  some  of  the  animals. 

7.  Usually  not  shock.  This  is  rather  surprising. 
I  have  taken  the  blood-pressure  in  two  patients 
whilst  four  or  five   nerve-roots  in  the  lumbar  and 

15 


226    THE    FUNCTIONS    OF    THE    SPINAL 

sacral  plexus  were  cut  on  each  side,  and  there  has 
been  no  sudden  fall.  There  was  a  steady  drop 
throughout  the  whole  operation  (under  open  ether 
anaesthesia)  amounting  to  less  than  eight  millimetres 
of  mercury. 

8.  Certain  degenerative  changes.  The  posterior 
columns  of  the  spinal  cord  show  Wallerian  degenera- 
tion running  up  to  their  termination  in  the  gracile 
and  cuneate  nuclei  of  the  medulla.  As  Warrington 
has  pointed  out,  in  animals  the  cells  of  the  anterior 
horn  on  the  same  level  as  the  severed  roots  show 
signs  of  chromatolysis,  or  dissipation  of  their  Xissl 
granules.  I  have  recently  been  able  to  demonstrate 
this  in  man.  A  patient  who  had  been  treated 
for  gastric  crises  by  resection  of  the  posterior  nerve- 
roots  from  the  seventh  to  the  tenth  dorsal,  died  about 
two  months  afterwards.  In  the  cervical  region  aU 
the  nerve-cells  were  normal,  but  in  the  region  of  the 
divided  roots  more  than  half  the  anterior  horn  cells, 
and  all  the  cells  of  Clark's  column,  showed  marked 
chromatolysis.  This  is  interesting  in  the  light  of 
the  various  affections  of  the  motor  functions  just 
mentioned. 

The  surgery  of  the  posterior  nerve-roots  is  yet  in 
its  infancy,  but  it  promises  to  have  a  future.  When 
it  is  resorted  to  earlier,  it  will  most  probably  have  a 
greater  value. 

There  are  two  main  indications  for  dividing  the 
posterior  nerve-roots.  The  one  is  pain,  and  the  other 
extreme  rigidity  in  the  course  of  spastic  paraplegia 
of  hemiplegia.  The  pain  may  be  due  to  such  a 
cause  as  the  crises  of  locomotor  ataxia,  or  the  agonies 


CORD     AND     PERIPHERAL     NERVES     227 

of  inoperable  cancer.     It  is  more  successful  for  the 
latter  than  for  the  former. 

When  many  roots  are  cut  for  spasticity,  it  is 
necessary  to  leave  one  or  two  intact,  or  a  very 
decided  amount  of  ataxy  may  be  induced.  The 
relief  of  adductor  or  other  spasm  is  often  very 
marked,  if  it  has  not  become  permanent  in  con- 
sequence of  fibrous  shortening  of  the  muscles  and 
tendons. 

INJURIES     AND     REPAIR     OF     PERIPHERAL 
NERVE. 

The  terrible  frequency  of  nerve  injuries  in  the 
war  has  given  a  fresh  impetus  to  the  study  of  these 
problems,  and  a  number  of  valuable  researches  have 
been  published  on  the  histology  of  regeneration  and 
on  other  points. 

One  of  our  greatest  difficulties  has  been  to  obtain 
reliable  evidence,  before  operation,  as  to  whether  a 
nerve  presenting  all  the  signs  and  symptoms  of 
complete  division  (paralysis,  anaesthesia,  and  the 
like)  was  as  a  matter  of  fact  cut  across,  or  partly 
divided,  or  merely  bruised  or  shocked.  We  found 
that  a  bullet  passing  near  but  not  through  a  nerve 
frequently  gave  rise  to  a  temporary  paralysis  of  all 
its  functions.  If  the  electrical  reactions  remained 
normal  (beyond  the  first  ten  days),  a  speedy  recovery 
might  be  expected,  but  in  very  many  cases  there 
was  reaction  of  degeneration  just  as  in  a  case  of 
anatomical  severance,  yet  the  functional  nature  of 
the  injury  would  be  proved  by  spontaneous  cure 
in   a   few   weeks'    time.     Electrical   testing  has   its 


228    THE    FUNCTIONS    OF    THE    SPINAL 

limitations.  Occasionally  normal  muscle  shows 
A.CC.  greater  than  K.C.C. 

In  practice  therefore,  in  such  doubtful  cases,  it 
became  customary  to  wait  about  three  months  to 
give  nature  every  chance.  Another  advantage  of 
waiting  was  that  it  gave  time  for  the  wound  to 
become  sterile.  Only  too  often  we  had  to  wait  not 
months  but  years  to  secure  asepsis,  without  which 
nerve  suturing  is  foredoomed  to  failure.  It  is  an 
interesting  question  just  when  this  waiting  rule 
ought  to  be  applied  to  nerve  injuries  in  civilian 
practice.  Even  after  three  months,  natural  recovery 
is  not  hopeless.  A  musculospiral  case  of  mine,  with 
complete  electrical  reactions  of  degeneration,  got 
well  quite  suddenly  after  nine  months  without 
operation.  In  some  of  these  patients  there  probably 
was  an  anatomical  division,  but  the  two  ends  of 
the  nerve,  being  in  apposition,  united  spontan- 
eously. 

A  new  test  has  been  introduced  by  Tinel,  called 
'  distal  tingling  on  percussion',  or  D.T.P.,  intended 
to  help  clear  up  the  diagnosis  in  these  cases.  If, 
shall  we  say,  the  ulnar  nerve  is  divided  in  the 
middle  of  the  upper  arm,  and,  after  several  months, 
tapping  the  ulnar  trunk  behind  the  internal  condyle 
at  the  elbow  sends  a  tingling  sensation  down  the 
arm  to  the  little  finger,  it  certainly  suggests  that 
new  nerve  fibres  have  grown  down  as  far  as  the 
elbow.  In  practice,  however,  I  have  found  the  sign 
gravely  misleading  more  than  once.  The  tapping 
may  be  transmitted  by  pulling  on  the  end  of  the 
nerve  above  the  injury  ;    also,  one  has  to  be  sure 


CORD    AND    PERIPHERAL    NERVES    229 

that  the  patient  has  not  discovered  that  if  he  says 
he  feels  the  tinghng  he  may  be  let  off  operation  ! 

The  only  reliable  test  is  to  explore  the  nerve  and 
stimulate  the  trunk  with  the  faradic  current  above 
and  below  the  lesion.  If  it  conducts,  it  will  recover  ; 
if  it  does  not,  the  scar  should  be  excised  and  the 
two  ends  sutured. 

Pain  and  mottling  of  the  skin  are  often  more 
marked  in  cases  of  partial  than  complete  division  of 
a  nerve. 

The  old  controversy  as  to  the  method  of  nerve- 
regeneration  is  now  definitely  settled  in  favour  of 
the  view  that  the  new  nerve-fibres  formed  after 
suture  are  budded  out  from  the  cut  central  end.  It 
will  be  found  that  new  medullated  fibres  are  present 
only  in  the  proximal  part  of  the  regenerating  nerve  at 
first,  whereas  at  a  later  date  they  reach  the  peripher>\ 
Only  a  few  millimetres  may  have  regenerated  in  a 
month.  It  has  recently  been  shown,  by  Perroncito, 
that  the  fine  fibrils  which  constitute  the  axis  cylinders 
of  the  central  end  commence  to  grow,  curl,  bud,  and 
branch  within  a  few  hours  of  the  injury,  apparently 
'  feeling  for  '  the  old  track. 

Mott  and  HaUiburton  have  shown  that  if  a  nerve 
is  cut  and  sutured,  and  time  allowed  for  regeneration, 
after  a  second  section  at  the  same  place  the  new 
medullated  fibres  peripheral  to  the  injury  all  degener- 
ate. Had  they  been  developed  in  situ  by  the  activity 
of  the  sheath-cells,  one  would  not  expect  degeneration 
after  the  second  section,  because  they  would  not  in 
that  case  have  been  cut  off  from  their  centre  of  origin. 
The  deduction  is  that  the  new  fibres  were  derived 
from  the  central  end. 


230    THE     FUNCTIONS     OF    THE     SPINAL 

Convincing  proof  has  been  advanced  by  embryo- 
logists  that  the  nerves  in  the  embryo  are  not  formed 
in  sitii,  but  are  budded  out  from  the  nervous  elements 
of  the  brain  and  spinal  cord.  By  removing  the 
medullary  groove  in  frog  embryos  and  planting  it 
in  lymph-clot,  Ross  Harrison  has  actually  observed 
the  developing  nerve-cell  grow  out  its  axon  at  the  rate 
of  20  fx  in  twenty-five  minutes.  The  outgrowing  axon 
is  activety  amoeboid.  He  was  able  also,  by  destrojdng 
the  ventral  part  of  the  developing  spinal  cord,  to 
obtain  tadpoles  in  which  the  muscles  had  no  motor 
nerves.  If  it  is  allowed  that  in  the  embryo  the  nerves 
grow  out  from  the  central  nervous  system,  the  theory 
of  central  regeneration  is  placed  upon  a  strong  basis. 

Two  questions  of  great  interest  have  recently 
received  answers.  First,  Why  does  the  medullary 
sheath  of  a  nerve-fibre  break  up  into  fatty  droplets 
when  it  is  cut  off  from  its  trophic  centre,  that  is 
from  its  cell  of  origin  in  the  central  nervous  system  ? 
Second,  How  does  the  budding  axis  cylinder  of  the 
central  end  of  a  divided  nerve  manage  to  find  its 
way  so  accurately  along  the  old  path  ? 

The  questions  are  intimately  related.  Each  fur- 
nishes the  answer  to  the  other.  The  medullary  sheath 
breaks  up  that  it  may  liberate  the  chemical  substance 
which  attracts  the  sprouting  axis  cylinder.  The  new 
fibre  follows  the  old  path,  because  of  the  chemical 
attraction  along  that  path. 

Nature  is  full  of  analogies  to  this  process  of  chemi- 
cal attraction.  Chemical  particles,  though  infinitely 
diluted  with  air  or  soil,  attract  the  vulture  to  the 
corpse  in  the  desert,  or  the  bloodhound  to  the  hunted 


CORD    AND    PERIPHERAL    NERVES    231 

i 
criminal.  Smell  is  only  a  chemical  analysis.  Simi- 
larly, the  leucocytes  crowd  out  of  the  vessels  to  an 
inflamed  area,  in  obedience  to  a  law  of  chemical 
attraction. 

If  two  celloidin  tubes  are  presented  to  the  central 
end  of  a  divided  nerve,  the  one  containing  emulsion 
of  liver,  and  the  other  emulsion  of  brain,  all  the 
sprouting  fibres  pass  into  the  brain  emulsion,  none 
into  the  tube  containing  liver  (Forssman).  The 
disintegration  of  the  nervous  matter  lays  down  a  line 
of  bait  to  entice  the  regenerating  fibres  along  paths 
of  usefulness. 

The  phenomena  of  repair  after  suture  next  call 
for  remark.  It  may  be  said  at  once  that  the  sooner 
the  operation  is  performed  the  better  will  be  the 
results.  If  the  muscles  have  ceased  to  contract  to 
any  form  of  electrical  stimulus,  operation  is  useless. 
It  is  very  seldom  that  benefit  will  be  obtained  if 
two  years  have  elapsed  since  the  injury.  Wlien 
secondary  suture  fails  to  give  a  good  result,  the 
fault  lies  not  with  the  degenerated  nerve-fibres  so 
much  as  with  the  nerve- cells  in  the  spinal  cord.  If 
asepsis  is  secured,  accurate  primary  suture  seldom 
if  ever  fails. 

Sherren,  before  the  war,  gave  average  time  relations 
as  follows  : — 

5-25  weeks  :  Commencing  return  of  protopathic 

sense. 
6-12  months  :   Complete  return  of  protopathic 

sense. 
12-18  months  :    Return  of  epicritic  sense. 
12-24  months  :   Motor  recovery. 


232    THE    FUNCTIONS    OF    THE    SPINAL 

Taking  the  ulnar  nerve  as  an  example,  recovery 
may  be  hoped  for  in  twelve  months  when  it  has  been 
divided  at  the  wrist,  or  in  twenty-four  months  when 
the  injury  was  at  the  elbow. 

These  figures  are  rather  on  the  slow  side,  judged 
by  our  experience  during  the  war.  According  to 
Burrow  and  Carter  the  average  for  the  ulnar  nerve 
(327  cases)  was  nine  months  ;  sensation  was  never 
perfectly  restored.  The  musculospiral  began  to 
improve  in  seven  to  eight  months  ;  complete  recovery 
was  seen  about  the  fifteenth  month.  In  cases  of 
median  nerve  injury  (242  cases)  the  forearm  flexors 
were  restored  in  eight  months,  and  the  intrinsic 
muscles  of  the  hand  in  fourteen  to  twenty  months. 

There  is  a  good  deal  of  variation,  for  some  unknown 
reason,  amongst  the  different  nerves.  The  musculo- 
spiral recovers  quickly  and  well  after  operation. 
The  ulnar  and  sciatic,  especially  the  internal 
popliteal,  are  relatively  slower  and  less  perfect.  It 
is  apparently  an  advantage  in  healing  that  a  nerve 
should  contain  principally  motor  fibres  and  not 
motor  and  sensory  mixed,  because  there  is  so  much 
the  better  chance  of  the  down-growing  motor  fibres 
finding  their  way  to  muscle  and  not  to  skin. 

In  general,  trophic  and  vasomotor  recovery  is 
the  first  to  appear,  then  deep  sensibility,  then  sensa- 
tions of  roughness  and  pressure  pain.  Radiating 
and  ill-localized  sensations  referred  to  wide  areas 
come  next,  then  these  give  place  to  sensibihty  to 
light  touch.  By  this  time  motor  power  is  generally 
returning  ;  it  may  come  quite  rapidly  within  a  few 
days,  and  usually  before  the  electric  responses  have 


CORD     AND     PERIPHERAL    NERVES     233 

returned  to  normal.  Stereognosis  returns  late  if  at 
all. 

Durin^^  recovery,  a  remarkable  phenomenon  has 
been  described  by  Trotter,  who  had  nerve  sections 
performed  upon  himself.  Any  stimulus  over  the 
cutaneous  area  affected,  gives  rise  to  a  decidedly 
painful  sensation,  referred  usually  to  the  most  distant 
part  of  that  area. 

Recovery  after  incomplete  division  of  a  nerve  is 
more  rapid,  usually  taking  less  than  six  months  for 
sensory  restoration  ;  it  is  perhaps  a  year  before 
motor  power  is  normal.  Protopathic  sense  does  not 
return  before  epicritic,  as  it  does  when  the  nerve  is 
completely  divided  ;  they  are  restored  side  by  side 
at  an  equal  rate. 

The  last  point  we  shall  consider  is  how  best  to 
proceed  when  so  much  nerve  has  been  lost  that  the 
ends  cannot  be  got  together.  Many  methods  have 
been  adopted,  some  of  which  are  of  little  or  no  value 
and  should  be  allowed  to  drop  out  of  use.  Amongst 
these  may  be  mentioned  the  introduction  of  a  bridge 
of  silk  or  catgut,  or  of  nerve  derived  from  a  cat,  dog, 
or  rabbit  (which  will  undergo  dissolution),  and  the 
device  of  splitting  the  nerve  longitudinally  and  turn- 
ing down  one-half  across  the  gap.  It  is  quite  evident 
why  these  fail.  The  silk,  catgut,  and  probably  the 
animal's  nerve,  cannot  provide  the  necessary  chemical 
attraction  for  the  down-growing  nerve-fibres.  The 
splitting  '  en-Y  '  does  not  lay  down  a  continuous 
'  scent '  along  the  tract  ;  it  is  broken  at  the  stem  of 
the  Y.  Better  results  may  be  obtained  by  suturing 
into  the  interval  a  length  of  human  nerve.     This 


234    THE     FUNCTIONS     OF    THE     SPINAL 

may  be  obtained  from  an  amputated  limb,  but 
it  is  always  possible  to  excise  several  inches  of  some 
unimportant  nerve  such  as  the  internal  cutaneous 
of  the  arm,  and  if  this  is  too  slender,  two  or  more 
pieces  may  be  used  parallel  to  one  another.  The 
nerve  can  be  located  before  the  anaesthetic  is  given 
by  testing  with  an  electric  current  ;  when  the 
electrodes  are  applied  over  the  nerve  a  tinghng  or 
pain  is  felt  throughout  its  distribution.  It  is  con- 
sidered by  some  to  be  an  advantage  to  protect  the 
nerve  junctions  from  invasion  by  fibrous  tissue  ; 
this  may  be  done  by  enclosing  them  in  a  ring  or  tube 
of  superficial  vein.  Probably  Cargile  membrane 
does  more  harm  than  good. 

There  is  yet  another  method,  which  is  sometimes 
the  only  one  available.  Langley  made  some  very 
interesting  experiments  on  the  effects  of  joining  up 
the  cut  ends  of  different  nerves,  and  found  that  their 
functions  could  be  transposed.  Thus  he  turned  the 
cat's  vagus  into  the  cer\dcal  sympathetic,  and  allowed 
regeneration  to  take  place.  The  vagus  is  of  course 
the  ner\'e  of  swallowing,  and  therefore,  whenever 
the  cat  lapped  milk,  all  the  effects  of  stimulation  of 
the  cervical  sympathetic  were  seen  on  the  side 
operated  on — dilatation  of  the  pupil,  starting  of  the 
eye,  sweating,  retraction  of  the  nictitating  membrane, 
pallor  of  the  ear,  bristling  of  the  hair,  and  quicken- 
ing of  the  heart-beat.  Wlien,  however,  the  (purely 
sensory)  lingual  nerve  and  the  (purely  motor)  hypo- 
glossal were  crossed  in  like  manner  there  was  no 
result. 

The  method  of  nerve  anastomosis  was  introduced 


CORD    AND    PERIPHERAL    NERVES    235 

into  practical  surgery  by  Ballance,  who  put  part  of 
the  spinal  accessory  nerve  into  the  peripheral  end 
of  the  degenerated  facial  nerve  to  relieve  intractable 
facial  palsy.  The  result  was  excellent,  but  there  was 
a  tendency  of  course  for  the  face  and  the  trapezius 
to  contract  together,  and  smiling  was  accompanied 
by  jerking  of  the  shoulder.  The  hypoglossal  is  now 
utilized  instead  of  the  spinal  accessory  to  avoid 
this.  It  was  hoped  that  there  was  a  wide  field  of 
usefulness  before  this  device  of  nerve  anastomosis, 
especially  in  infantile  palsy.  For  instance,  if  the 
anterior  tibial  muscles  and  peronei  alone  were 
affected,  the  external  popliteal  might  be  divided  and 
the  peripheral  end  put  into  a  notch  in  the  internal 
popliteal.  Unhappily,  published  results  are  very 
disappointing,  at  any  rate  in  the  case  of  infantile 
paralysis  ;  probably  even  the  anterior  horn  cells 
supptying  useful  muscles  have  been  somewhat 
damaged,  and  cannot  take  on  more  than  ordinary 
work. 

Our  war  experience  has  shown  us  that  direct 
end-to-end  suture  of  nerves  is  much  superior  to 
either  nerve  grafting  or  nerve  transplantation.  Some 
surgeons  consider  that  both  these  devices  are  useless. 
We  still  await  adequate  lists  of  published  end-results 
to  enable  us  to  decide  the  question.  I  have  followed 
through  eight  cases  in  which  I  bridged  a  gap  by 
transplanting  two  or  three  plies  of  the  internal 
cutaneous  nerve.  Two  were  successful  (a  musculo- 
spiral  and  an  external  popliteal)  ;  six  probably  or 
certainly  failed.  Nerve  anastomosis  suffers  from 
the  drawback  that  notching  the  sound  trunk  may 


236  PERIPHERAL    NERVES 

cause  some  paralysis  of  muscles  that  before  the 
operation  were  intact  ;  it  is  said  that  if  no  more 
than  one-third  of  a  trunk  is  divided,  no  paralysis 
follows,  but  only  a  very  \\dde  experience  of  notching 
every  nerve  in  the  body  and  in  every  part  of  their 
courses  could  justify  such  a  statement. 

Various  de\dces  of  position  may  be  made  use  of 
to  get  the  two  ends  of  a  nerve  together  across  the 
gap,  such  as  acutely  flexing  the  knee  for  the  sciatic  ; 
such  a  ner\^e  as  the  ulnar  may  wdth  great  advantage 
be  displaced  from  behind  the  condyle.  These  pro- 
cedures, whenever  possible,  are  much  to  be  preferred 
to  nerve  transplantation,  and  even  more  to  nerve 
anastomosis.  Some  surgeons  think  it  justifiable  to 
resect  the  humerus  and  shorten  it  an  inch,  so  as  to 
get  the  ends  of  a  nerve  together.  Sometimes,  in  the 
case  of  the  musculospiral,  a  good  result  may  be  ob- 
tained by  letting  the  nerve  alone,  and  transplanting 
the  tendons  of  the  flexor  carpi  radialis,  palmaris 
longus,  and  flexor  carpi  ulnaris  into  the  extensors  of 
the  thumb  and  fingers. 

REFERENCES. 

Walshe. — Brain,   1919,  xlii,  p.   i. 

Ramsay  Hunt. — Brain,   1918,  xli,  p.  302. 

Ransom. — Amer.  Jour,  of  Physiol.,  1916,  xl,  p.  571. 

RiDDOCH. — Brain,   1918. 

FoRSTER. — Zeitschrift  f.  orthopdd.  Chir.,  190S,  Bd.  xxii,  p.  203. 

Head  and  Thompson. — "  The  Grouping  of  Afterent  Impulses 

in  the  Spinal  Cord,"  Brain,  1906,  p.  537. 
A.    Rendle    Short. — Proc.    Royal   Soc.    Medicine,    Surgical 

Section,  July,  191 1. 
Sherrington. — Integrative  Action    of  the    Nervous    Sysian. 
Eloesser. — Ann.  Surg.,  1917,  p.  201. 


237 


CHAPTER    XII I. 

LOCALIZATION     OF     FUNCTION     IN 
THE     BRAIN. 

LOCALIZATION  OF  SENSATION  IN  THE  CEREBRAL  CORTEX  ; 
VISION,  HEARING,  CUTANEOUS  AND  OTHER  FORMS  OF 
SENSATION  — FUNCTIONS       OF     THE      FRONTAL      CORTEX  — 

APRAXIA — APHASIA MISLEADING    LOCALIZING     SIGNS     OF 

INTRACRANIAL  TUMOUR OPTIC  NEURITIS — THE  CERE- 
BELLUM— TUMOURS  IN  THE  CEREBELLO-PONTINE  ANGLE 
THE     CEREBROSPINAL    FLUID. 

THE  large  number  of  cases  of  localized  injury  to 
the  brain  occurring  in  the  war  have  given  a 
decided  impetus  to  neurology.  Painstaking  investi- 
gations, of  much  larger  groups  of  examples  of  a 
particular  injury  than  civil  practice  could  furnish, 
have  been  carried  out  by  the  most  competent 
observers.  Some  of  the  results  are  given  in  this 
chapter. 

LOCALIZATION  OF  SENSATION  IN  THE 
CEREBRAL  CORTEX. 

Vision. — It  has  long  been  known  that  visual 
sensations  are  received  on  the  mesial  surfaces  of  the 
occipital  lobes,  just  above  and  below  the  calcarine 
fissure.  Histologically,  the  area  is  mapped  out  by 
the  white  line  of  Gennari,  which  is  a  lamella  of 
medullated  fibres  splitting  the  grey  cortex,  and  by 
the  occurrence  in  the  pyramidal  layers  of  certain 


238        LOCALIZATION    OP    FUNCTION 

stellate  cells.     This  area  slightly  encroaches  on  the 
convexity   of  the  hemisphere  at   the  occipital  pole. 

This  calcarine  area  is  called  the  visttosensory 
cortex.  For  the  interpretation  of  things  seen  we 
are  dependent  on  the  outer  surface  of  the  occipital 
cortex,  the  so-called  visuopsychic  area. 

It  is  well  known  that  the  right  half  of  each  retina 
(that  is,  the  nasal  half  of  the  left  retina  and  the 
temporal  half  of  the  right)  is  represented  in  the 
right  visuosensory  area.  Gordon  Holmes  and  Lister 
have  shown  that  a  lesion  of  the  upper  lip  of  the  cal- 
carine fissure  causes  blindness  of  the  upper  half  of 
each  retina.  This  confirms  previous  work.  There- 
fore a  lesion  of  the  left  cortex  above  the  calcarine 
fissure  would  render  the  upper  left  quadrant  of  each 
eye  blind  ;  the  patient  would  not  be  able  to  see  his 
right  foot  when  sitting  in  a  chair  and  looking 
straight  forwards. 

Further,  they  show  that  the  macula,  the  point  of 
most  acute  vision,  with  which  we  read,  is  represented 
in  the  little  piece  of  visual  cortex  which  overlaps 
the  convexity  of  the  hemisphere  behind,  and  at 
the  posterior  end  of  the  calcarine  fissure.  The 
representation  is  not  bilateral,  as  used  to  be  taught. 
If  a  bullet-track  destroys  the  rest  of  the  calcarine 
area  but  leaves  the  posterior  poles  intact,  the  patient's 
world  looks  as  if  seen  through  a  telescope ;  the 
periphery  is  cut  off. 

Further,  it  is  shown  that  each  region  of  the  visuo- 
sensory area  corresponds  to  a  region  of  the  two 
retinae,  which  always  work  together.  That  is  to 
say,  if  the  right  calcarine  fissure  be  taken  as  repre- 


IN     THE     BRAIN  239 

sented  by  the  English  Channel  on  the  map,  the 
North  Sea  standing  for  the  occipital  pole,  then  Dover 
and  Calais  correspond  to  the  region  for  the  macula  ; 
Sussex  and  Hampshire,  representing  the  sloping 
sides  of  the  upper  lip  of  the  fissure,  correspond  to 
areas  in  each  retina  traversed  by  a  line  running 
from  the  macula  horizontally  to  the  right ;  and 
going  up  the  Thames  Valley,  which  represents  the 
upper  limits  of  the  visuosensory  area,  corresponds 
to  areas  in  the  retinae  traversed  by  a  line  drawn 
vertically  upwards  from  the  macula — the  higher  on 
the  cortex  equals  the  higher  on  the  retina,  and  the 
further  forwards  on  the  cortex  equals  the  nearer  the 
periphery  of  the  retina. 

Lesions  of  lateral  surfaces  of  both  hemispheres, 
the  visuopsychic  cortex,  involving  the  angular, 
supramarginal,  post-parietal,  and  occipital  regions, 
give  rise  to  loss  of  perception  of  size,  depth,  and 
distance,  inability  to  recognize  the  nature  of  objects, 
and  impairment  of  convergence  and  accommodation. 

Hearing. — Although  it  is  certain  that  monkeys 
which  have  suffered  bilateral  removal  of  the  temporal 
cortex  give  every  external  e\adence  that  they  can 
hear,  it  is  very  difficult  to  be  equally  certain  that 
sounds  are  still  appreciated  in  consciousness  by  them, 
and  recognized  for  what  they  signify.  It  is  no  more 
evidence  of  conscious  hearing  that  a  monkey  looks 
round  when  a  bell  sounds,  than  it  is  of  conscious  pain 
that  a  man  with  a  fractured  spine  withdraws  a  foot 
pricked  by  a  pin.  It  might  be  a  reflex  from  a  lower- 
level  centre,  such  as  the  posterior  corpus  quadri- 
s^eminum.     Recently  the  whole  cerebral  cortex  has 


240        LOCALIZATION    OF    FUNCTION 

been  removed  on  both  sides  in  monkeys  (Macacus). 
One  lived  twenty-six  days.  They  stiU  responded 
to  noises  by  movements  of  the  body  and  ears. 
Stimulation  of  the  temporal  cortex  in  monkeys 
causes  pricking  up  of  the  ears. 

At  any  rate,  there  is  a  fair  amount  of  human 
evidence,  both  anatomical  and  clinical,  to  locate  this 
function  in  the  temporal  convolutions  and  island  of 
Reil,  and  none  to  locate  it  elsewhere.  Fibres  from 
the  posterior  corpus  quadrigeminum,  and  some  from 
the  lateral  fillet,  which  is  well  known  to  come  from 
the  cochlear  nuclei,  ma}^  be  traced  to  this  part  of  the 
cortex.  Deafness  and  abnormal  auditory  sensations 
have  been  associated  with  disease  of  this  region. 
Perhaps  the  most  convincing  observation  on  record 
was  made  by  Harvey  Gushing,  who  stimulated  the 
exposed  temporal  cortex  in  a  conscious  man,  and  the 
patient  said  that  he  heard  a  buzzing  noise. 

There  are  cases  on  record  of  complete  bilateral 
destruction  of  the  temporal  cortex  with  persistence 
of  the  island  of  Reil,  and  normal  hearing.  This  may 
indicate  that  the  island  is  more  important  as  an 
auditory  centre  than  the  temporal  convolutions. 

Cutaneous  and  Other  Forms  of  Sensation. — 
The  great  war  has  provided  a  wealth  of  clinical 
material  for  the  study  of  those  problems  relating 
to  the  cerebral  localization  of  the  various  forms  of 
sensation  derived  from  the  limbs,  which  used  to  be 
so  controversial.  On  this  subject  experiments  on 
animals  could  give  little  or  no  information.  Enormous 
lesions  in  monkeys  were  found  to  cause  hemianaes- 
thesia,   but  smaller  removals  gave  rise  to  little  if 


IN    THE    BRAIN  241 

any  defect  of  sensation.  Sherrington  has  recently 
removed  parts  of  the  postcentral  cortex  in  a  chim- 
panzee. The  animal  was  not  tame  enough  to  allow 
detailed  examination  of  its  sensations  afterwards, 
but  there  was  no  loss  to  the  coarser  methods  of 
testing. 

Gushing  excited  the  postcentral  convolution  in 
two  conscious  patients  who  had  previously  been 
trephined,  by  unipolar  faradic  stimulation.  He 
found  that  the  brain  itself  was  devoid  of  any  sort 
of  feeling,  but  that  sensations  of  stroking,  tingling, 
or  warmth  were  produced,  referred  to  the  hand  of 
the  opposite  side.  The  sensation  was  quite  well 
defined  and  localized  ;  one  area  corresponded  to  the 
index  finger,  and  another  to  the  back  of  the  hand. 
When  the  electrode  was  applied  in  front  of  the  fissure 
of  Rolando  instead  of  behind,  the  fingers  or  hand 
moved,  but  there  was  no  sensation.  An  incision  in 
the  postcentral  convolution  was  quite  painless,  and 
caused  some  numbness  of  all  forms  of  sensation  in 
the  hand. 

Many  years  ago,  before  it  was  realized  that  the 
convolutions  in  front  of  and  behind  the  fissure  of 
Rolando  differed  in  function.  Ransom  and  also 
Laycock  observed  that  a  tingling  sensation  was 
elicited  when  they  stimulated  the  exposed  cortex  in 
a  conscious  man,  and  apparently  they  both  applied 
the  electrodes  in  front  of  the  fissure  ;  Gushing  and 
others  have  failed  to  confirm  this.  Recently  Sir 
Victor  Horsley  published  an  account  of  the  only 
case  in  which  he  had  removed  a  cortical  centre  (part 
of  the  hand   area)   without   encroaching  upon   the 

16 


242        LOCALIZATION    OF    FUNCTION 

ascending   parietal   gyrus    (for   athetosis).     Immedi- 
ately after  the  operation  there  was  complete  flaccid 
paralysis   of   the   arm   and   some   interference   with 
sensation.      The   hand   could   detect   cold  but   not 
warmth,  stroking  with  a  wool  pencil  was  not  felt 
on  the  ungual  phalanges,  there  were  inaccuracy  of 
location  of  pain  and  touch  and  loss  of  the  sense  of 
position,  and  objects  placed  in  the  hand  were  not 
recognized  by  touch  (astereognosis).     A  year  later, 
movement  was  recovered,   except  for  some  spastic 
paralysis  in  the  two  ulnar  fingers  ;    there  were  still 
astereognosis,    inaccuracy    of    location,    and    slight 
dulling  of  sensation  over  the  ulnar  border  of  the 
hand.     If  the  lesion  had  involved  the  postcentral 
cortex,  the  sensory  disturbance,   in  his  experience, 
would  have  been  much  more  marked.     The  athetosis 
movements  were  cared. 

It  is  quite  certain  that  lesions  in  man  involving 
the  ascending  parietal  (postcentral)  convolution 
almost  always  cause  some  interference  with  sensa- 
tion, more  so  than  defects  of  any  other  parts  of 
the  cortex  would  do.  There  is  never  complete 
anaesthesia,  except  just  after  an  epileptic  convulsion 
or  injury,  or  in  hysteria.  Further,  it  is  proved  that 
the  leg  area  is  nearest  the  top,  the  arm  area  next, 
and  that  for  the  face  lowest,  corresponding  to  the 
distribution  in  the  precentral  (motor)  convolution. 
Bergmark  quotes  thirty-three  cases  of  lesions  of  the 
postcentral  gyrus  with  sensory  symptoms  but  no 
paralysis. 

Dr.   Head  has  re-investigated  the  whole   subject, 
using  a  large  number  of  wounded  officers  and  men  as 


IN    THE    BRAIN  248 

clinical  material.  The  results  are  interesting  and 
important.  The  more  primitive  sensations,  those 
possessed  by  most  vertebrates,  such  as  tactile,  heat, 
and  cold,  are  appreciated  by  the  optic  thalamus, 
which  represents  the  primitive  sensory  cortex.  It  is 
the  optic  thalamus,  also,  that  gives  emotional  colour 
to  the  sensations — that  regards  some  as  pleasurable, 
and  others  as  painful.  Obviously  pleasure  and 
pain  are  very  primitive  sensations.  The  degree  of 
pleasure  excited  by,  shall  we  say,  gentle  stroking 
or  a  spray  of  warm  water,  and  the  degree  of  pain 
excited  by  a  pinprick,  are  partially  damped  down 
by  impulses  derived  from  the  cortex.  Fibres  from 
all  parts  of  the  cortex  converge  on  the  lateral  nucleus 
of  the  thalamus,  and  tend  to  control  and  inhibit 
excessive  pain  or  pleasure  arising  from  impulses 
received  from  the  spinal  cord.  When  this  lateral 
nucleus  is  damaged,  and  only  the  mesial  part  of 
the  thalamus  is  left  intact,  pinpricks  are  much  more 
painful,  and  stroking  or  warmth  more  pleasant,  than 
on  the  normal  side.  Sometimes  music  produces  a 
remarkable  emotional  effect  in  the  affected  limbs, 
especially  if  it  is  solemn  and  majestic.  A  complete 
destruction,  say  of  the  right  optic  thalamus,  produces 
hemiansesthesia  of  the  left  side  of  the  body,  with 
blindness  of  the  right  half  of  each  retina,  sometimes 
athetosis,  and  a  curious  form  of  facial  paralysis. 
When  the  pyramidal  tract  is  injured,  causing  hemi- 
plegia, voluntary  movements  of  the  face  are  impaired 
but  emotional  movements  persist — a  smile  or  an 
involuntary  frown  are  still  symmetrical.  When  the 
thalamus    is    damaged,    voluntary    movements    are 


244        LOCALIZATION    OF    FUNCTION 

retained  but  the  emotional  movements  are  no  longer 
symmetrical.  The  explanation  is  that  the  emotional 
movements  are  of  primitive  origin,  and  therefore 
controlled  by  the  more  primitive  optic  thalamus, 
not  by  the  cortex. 

A  lesion  of  the  postcentral  cortex,  therefore,  does 
not  cause  complete  anaesthesia,  or  abolish  any  of 
the  senses  of  heat,  cold,  touch,  or  pain,  because 
these  are  apprehended  by  the  thalamus.  The 
function  of  the  sensory  cortex  is  not  merely  to 
receive  sensory  messages,  but  to  interpret  them. 
If  I  hold  a  glass  of  hot  water  in  my  hand,  the 
thalamus  tells  me  that  it  is  touching  my  hand,  that 
it  is  hot,  that  it  is  unpleasantly  hot  ;  the  middle 
part  of  the  postcentral  cortex,  behind  the  motor 
area  for  the  arm  and  hand,  tells  me  that  it  is  a 
smooth  round  glass,  that  it  weighs  so  many  ounces, 
and  that  it  is  of  such  and  such  a  size. 

Lesions  of  the  postcentral  cortex  in  the  arm  area 
produce  the  follo^ving  disabilities.  Certain  fingers 
are  affected,  others  are  normal. 

1.  Sensations  are  very  irregular  and  easily  fatigued. 
A  light  touch  or  other  means  of  testing  is  appre- 
ciated better  at  one  time  than  another. 

2.  Recognition  of  space  is  very  defective.  The 
patient  cannot  recognize  how  much  his  fingers  have 
been  moved  by  the  physician,  he  locahzes  badly, 
and  two  compass  points  are  interpreted  as  one  unless 
greatly  spaced  out  on  the  skin  tested. 

3.  He  cannot  judge  weights,  or  compare  shapes 
and  sizes,  or  tell  the  difference  between  silk,  velvet, 
cloth,  and  the '  like.     When  there  is  marked  inter- 


IN     THK     BRAIN  245 

ference  with  sensation  from  a  postcentral  injury, 
muscular  tone  is  deficient  in  the  corresponding 
part. 

We  can  go  some  way  towards  localization  of  these 
functions.  A  little  loss  of  sensation  may  be  pro- 
duced by  a  lesion  of  the  precentral  gyrus,  much  more 
by  injury  of  the  postcentral,  and  some  if  the  parietal 
convolutions  just  behind,  and  the  angular  gyrus, 
are  involved.  These  constitute  the  sensory  area 
of  the  cortex.  The  little  finger  is  represented  nearer 
the  leg  area,  the  thumb  nearer  the  face  area. 
Lesions  of  the  precentral  cortex  particularly  affect 
spacial  sense  ;  those  of  the  postcentral  gyrus  have 
the  greatest  effect  on  judgements  of  weight  and 
shape  ;  marked  disturbance  of  tactile  sense  indicates 
a  lesion  farther  back  or  in  the  angular  gyrus,  which 
may  also  interfere  with  temperature  sense.  It  will 
be  remembered  that  Sir  Victor  Horsley's  case  of 
excision  of  the  motor  area  for  the  hand  had  difficulty 
in  localizing. 

In  reference  to  the  views  which  have  just  been 
explained  with  regard  to  the  emotional  function  of 
the  optic  thalamus,  it  is  interesting  to  mention  that 
Graham  Brown  has  shown  that  stimulation  of  this 
nucleus  in  a  chimpanzee  gives  rise  to  the  movements 
which  constitute  laughter  in  apes. 

FUNCTIONS  OF  THE  FRONTAL  CORTEX. 

It  is  well  known  that  the  great  motor  centres  are 
limited  to  the  ascending  frontal  or  precentral  con- 
volution. This  has  been  abundantly  proved  by 
many  methods  :   by  the  study  of  paralysis  following 


246        LOCALIZATION    OF    FUNCTION 

localized  lesions  in  man,  or  removals  in  man  or 
apes  ;  by  electrical  stimulation  in  man  and  apes  ; 
and  histologically  by  the  limitation  to  this  region 
of  the  giant  pyramidal  or  Betz  cells,  which  are  the 
only  cells  to  undergo  chromatolysis  when  the  pyra- 
midal tracts  are  destroyed  in  the  spinal  cord. 

The  whole  field  of  the  observations  on  great  apes 
has  recently  been  gone  over  again  by  Sherrington 
and  Ley  ton,  using  a  truly  generous  amount  of 
material — three  gorillas,  three  orang-outans,  and 
twenty-two  chimpanzees.  They  give  wonderful  de- 
tailed diagrams  of  the  exact  spots  that  have  to  be 
stimulated  to  produce  particular  movements.  They 
make  a  point  that  the  cortex  must  not  be  allowed 
to  cool,  or  the  reactions  no  longer  appear.  After 
ablations  of  parts  of  the  motor  area,  paralysis  of 
course  ensues,  but  there  is  a  remarkable  degree  of 
recovery  in  a  few  days. 

It  often  becomes  of  great  importance  to  the  surgeon 
to  know  whether  a  tumour  causing  hemiplegia  is 
accessible,  either  in  the  cortex  or  close  beneath  it, 
or  inaccessible,  in  the  internal  capsule  or  isthmus. 
The  principal  evidences  of  the  former  are  the  occur- 
rence of  monoplegias,  the  face,  arm,  or  leg  being 
affected  alone  without  the  others,  whereas  lesions  of 
the  internal  capsule  would  paralyze  all  three  ;* 
secondty,  persistent  aphasia  may  be  present  ;  and 
thirdly,   there  may  be  recurring  con\ailsions.     The 


*  In  monkeys  the  fibres  to  the  head,  arm,  and  leg  are  grouped 
in  bundles  in  the  internal  capsule,  but  apparently  this  is  not  the 
case  in  man,  and  consequently  small  lesions  cause  mild  hemiplegia, 
not  monoplegia. 


IN     THE    BRATX  247 

degree  of  sensory  impairment  is  not  of  much  assist- 
ance, but  the  considerations  just  advanced  may 
sometimes  be  helpful. 

There  is  a  good  deal  of  evidence  that  if  the  paralysis 
is  of  a  flaccid  type  the  lesion  is  most  probably 
cortical,  though  the  converse  is  not  necessarily  true. 
In  man,  a  cortical  lesion  is  often  (not  always)  accom- 
panied by  a  flaccid  paralysis  with  no  Babinski  sign 
and  with  normal  or  diminished  reflexes  (see  cases 
quoted  by  Bergmark),  but  v/hen  the  optic  thalamus 
and  internal  capsule  are  involved,  there  is  always 
marked  rigidity.  This  subject  has  been  referred  to 
in  the  preceding  chapter. 

It  is,  however,  true  that  irritation  of  the  cortex, 
such  as  may  be  present  just  after  a  traumatic  lesion, 
or  during  the  growth  of  a  tumour,  may  cause  early 
contracture,  so  we  should  regard  the  presence  of 
rigidity  as  an  equivocal  sign,  but  absence  of  rigidity 
as  evidence  of  a  cortical  lesion. 

The  frontal  cortex  lying  in  front  of  the  motor  region 
is  described  as  a  '  silent  area  ',  and  extensive 
tumours,  degenerations,  or  injury  may  produce  few 
or  no  symptoms.  In  a  case  under  the  writer's  care,  a 
wound  one  inch  deep  into  the  brain,  from  the  vertex 
to  the  nose,  caused  by  a  chopper,  made  absolutely 
no  difference  to  the  woman's  character,  capacity, 
or  intelligence,  and  indeed  produced  no  symptoms 
at  all  beyond  concussion,  although  she  was  under 
observation  for  many  months.  In  the  famous 
American  crowbar  case,  where  a  large  part  of  the 
frontal  cortex  on  both  sides  was  destroyed,  there  was 


248        LOCALIZATION    OF    FUNCTION 

no  paralysis,  but  on  returning  to  work  the  man, 
previously  a  capable  foreman,  had  become  weak, 
vacillating,  inattentive,  and  profane.  There  are 
quite  commonly  signs  of  mental  dullness  in  patients 
with  frontal  lesions.  In  cats  there  are,  after  excisions 
of  the  frontal  cortex,  changes  in  the  disposition, 
and  recently  acquired  tricks  may  be  lost. 

Stimulation  of  this  region,  in  Sherrington  and 
Ley  ton's  anthropoid  apes,  produced  nothing  but 
de\iations  of  the  eyes  and  opening  of  the  lids. 
Similar  results  were  got  by  stimulating  the  occipital 
cortex. 

According  to  Sir  Victor  Horsley,  abscesses  of  the 
brain  invohdng  the  Rolandic  area  usually  lead  to  a 
raised  temperature  on  the  opposite  side  of  the  body, 
whereas,  if  the  location  is  in  front  of  or  behind  this 
region,  the  temperature  is  subnormal. 

APRAXIA. 

More  definite  evidence,  however,  is  now  available. 
There  are  a  number  of  carefuUy  studied  cases  on 
record  in  which,  with  no  actual  paralysis,  there  has 
been  a  remarkable  clumsiness  in  the  performance  of 
movements  requiring  any  skiU,  and  in  which  the 
patient  has  been  quite  unable  to  make  some  movement 
voluntarily  or  in  response  to  command,  although  he 
may  unconsciously  do  that  ver\^  thing  under  the 
influence  of  emotion  or  by  accident.  This  condition 
is  called  apraxia.  It  is  most  convincing  when  it  is 
unilateral.  Thus,  a  musician  may  lose  the  power  of 
pla3dng  his  instrument,  or  the  clerk  his  power  of 
writing.     In  Liepmann's  classic  case,  one  of  the  first 


IN     THE    BRAIN  249 

to  be  described,  there  was  apraxia  of  the  right  arm 
and  leg.     "  Asked  to  put  his  right  forefinger  on  his 
nose,  he  said,  'Yes',  and  with  his  stretched  forefinger 
executed  wide  circHng  movements  in  the  air.     He 
made  the  correct  movement  at  once  with  his  left 
hand.     Asked  to  close  his  right  hand  into  a  fist, 
he  performed  various  absurd  movements  of  his  arm 
and  body,  but  attained  the  required  goal  at  once  with 
his  left  hand.     When  asked  to  give  the  examiner 
a  certain  object  with  his  right  hand,  he  frequently 
picked  up  the  wrong  thing,  and,  still  holding  it  in 
his  hand,  used  the  left  to  take  up  the  required  object 
and  present  it  to  the  physician".    A  patient  of  de 
Buck's,  asked  to  hft  her  right  arm,  crossed  it  over 
her  body,  put  it  in  her  left  axilla,  and  after  making 
various  other  vigorous  but  futile  efforts,  said  plain- 
tively,   "  Je   comprends   bien   ce   que   vous   voulez, 
mais  je  ne  parviens  pas  a  le  faire  "  :  this  just  expresses 
the  condition. 

In  some  of  the  cases,  there  is  imperfect  recognition 
of  objects  or  of  their  uses  (agnosia),  but  these  are 
compHcated  and  cannot  be  described  here. 

It  is  an  important  fact  that  apraxia  of  the  left 
arm  is  common  in  right  hemiplegics,  whereas  apraxia 
of  the  right  arm  rarely  occurs  in  left  hemiplegics  ; 
moreover,  in  the  cases  where  there  is  apraxia  of  the 
left  side  with  hemiplegia  of  the  right,  there  is  evidence 
that  the  lesion  is  cortical,  not  in  the  internal  capsule. 
Thus  Liepmann  examined  eighty-three  hemiplegic 
patients,  with  these  results  : — 

Forty-two  had  left  hemiplegia  ;  they  could  neariy 
all  obey  directions  with  the  right  arm. 


250        LOCALIZATION    OF    FUNCTION 

Forty-one  had  right  hemiplegia  ;  of  these,  20  had 
apraxia  of  the  left  arm,  and  14  in  this  group  also 
had  aphasia  (therefore  the  lesion  was  cortical)  ;  21 
had  no  apraxia,  and  of  these  only  4  had  aphasia  (in 
most  of  the  other  17  cases  the  lesion  was  probably  in 
the  internal  capsule). 

Of  course,  as  left-handed  persons  form  one- 
twentieth  of  the  community,  it  is  possible  to  find  a 
few  cases  of  left  hemiplegia  with  right  apraxia. 

There  is  good  ground,  then,  for  believing  that  the 
centres  which  consciously  initiate  voluntary  move- 
ments for  both  sides  of  the  body  are  limited  to  the 
left  cortex  in  right-handed  people,  and  that  the 
precentral  convolutions  are  merely  the  departure 
platforms  for  messages  from  the  brain  to  the  cord. 
Instructions  are  sent  to  the  right  precentral  convolu- 
tion by  way  of  the  corpus  cailosum.  It  is  still  in 
doubt  whether  the  above-mentioned  initiating  centre 
is  in  the  left  precentral  gyrus,  or  whether  it  lies  in 
front  oj  this,  in  the  first  and  second  frontal  convolu- 
tions, as  most  neurologists  maintain.  It  is  quite 
certain  that  a  lesion  of  the  front  part  of  the  corpus 
cailosum  is  characterized  by  apraxia  of  the  left  arm  ; 
this  important  discovery  may  well  lead  to  successful 
surgical  removal  of  tumours  there  situated.  A  lesion 
in  the  left  frontal  cortex  may  cause  apraxia  of  both 
arms ;  there  will  probably  be  right  hemiplegia  as 
well,  which  would  mask  the  condition  in  the  right 
arm. 

To  sum  up,  a  lesion  is  cortical  if  there  are 
present : — 

I.  A  monoplegia. 


IN    THE    BRAIN  251 

2.  Hemiplegia  with  either  (a)  x\phasia  which 
persists  ;  (b)  Recurring  convulsions  ;  (c)  Flaccidity  ; 
(d)  Apraxia  of  the  opposite  side. 

Left-sided  apraxia  without  hemiplegia  indicates  a 
lesion  of  the  corpus  callosum. 

APHASIA. 

The  various  types  of  aphasia  have  always  presented 
problems  of  great  complexity  but  of  much  interest. 
Recent  studies  of  the  subject  have  been  very  revolu- 
tionary' in  their  tendency.  We  used  to  learn  that 
there  were  three  main  centres  for  the  appreciation 
and  utterance  of  language,  namely  : — 

1.  The  motor  centre,  controlling  utterance,  in 
Broca's  convolution  (the  third  left  frontal). 

2.  T^ie  auditory  word  centre,  appreciating  spoken 
language,  in  the  posterior  part  of  the  second  left 
temporal  convolution.  This  was  also  regarded  as 
dominating  and  being  necessary  for  the  activity  of 
the  other  two  centres. 

3.  The  visual  word  centre,  appreciating  written 
language,  in  the  left  angular  gyrus,  behind  and  above 
the  auditory  word  centre. 

Recently,  however,  the  searching  analyses  of  Marie 
and  his  pupils  have  raised  ver\'  grave  doubts  about 
the  first  and  third  of  the  above,  and  many  neuro- 
logists have  agreed  that  Broca's  convolution  has  no 
speech  function  at  all ;  very  few  now  defend  the 
existence  of  a  separate  \'isual  word  centre. 

Briefly,  the  contention  of  Marie  and  Moutier  may 
be  put  thus.  Between  1861  and  1906,  there  have 
been  pubUshed  304  cases  of  aphasia  with  autopsy. 


252        LOCALIZATION    OF    FUNCTION 

Of  these  201   were  useless   and   103   were  relevant. 


Useless 


Relevant 


Favourable  to 
Broca's  local- 
ization 


Unfavourable 
to  Broca's 
localization 


175 
26  201 


II      19 


(Lesion  too  extensive 

^  Badly  described        .... 

Cortical  lesions  with 
aphasia 

Subcortical    lesions 
with  aphasia 

Aphasia,  but  Broca's 
convolution  normal  57 

No  aphasia,  but 
Broca's  convolu- 
tion destroyed  (in 
two  cases,  bilateral 
destruction)  -          -     27     84 


304 

The  majority  even  of  the  nineteen  cases  allowed 
by  these  writers  they  consider  to  be  inconclusive 
for  various  reasons. 

Two  cases  of  Burckhart's  are  of  sufficient  surgical 
interest  to  be  worth  quoting.  In  the  first,  he  removed 
5  grms.  of  grey  matter  from  the  foot  of  the  first  and 
second  left  temporal  gyri,  but  no  word-deafness 
resulted.  Eight  months  later  he  resected  the  cap 
and  foot  of  the  left  third  frontal  gjnnis  (Broca's 
convolution),  but  no  aphasia  followed.  In  the  second 
case  he  resected,  in  several  operations,  the  left 
supramarginal,  temporal,  and  third  frontal  gyri, 
but  he  failed  to  induce  any  speech  defect.  The 
patients  were  demented,  with  verbal  delusions  and 
logorrhoea. 

Sherrington  and  Leyton  removed  Broca's  area 
in  a  particularly  vociferous  chimpanzee,  but  the 
operation  did  not  quiet  it  at  all. 

Marie   maintains    further    that    all    patients    with 


IX     THK     BRAIN  258 

aphasia  are  mentally  deficient  ;  thus,  the  cook  can 
no  longer  compound  an  omelette,  and  the  pianist 
can  no  longer  play  the  piano.  He  locates  all  the 
speech  functions  diffusely  in  the  left  temporo- 
parietal region,  maintaining  that  this  is  merely  a 
region  of  intelUgence  speciaUzed  for  language,  and 
not  a  storehouse  of  sensory  images  ;  a  mild  lesion 
destroys  the  function  last  acquired,  viz.,  reading, 
and  a  severer  lesion  produces  loss  of  voluntary 
speech  and  of  recognition  of  spoken  language  as  well. 
What  Marie  calls  '  anarthria  ' — a  word  previously 
used  in  another  sense — meaning  loss  of  the  power  to 
utter  speech,  although  the  individual  can  say  the 
words  over  to  himself,  is  due  to  a  lesion  in  '  the 
quadrilateral  ',  bounded  in  front  and  behind  by  the 
anterior  and  posterior  hmiting  sulci  of  the  island  of 
Reil,  internally  by  the  wall  of  the  lateral  ventricle, 
and  externally  by  the  surface  of  the  island  of  Reil. 
In  most  cases  of  so-called  Broca's  aphasia,  both  the 
temporal  cortex  and  the  '  quadrilateral  '  are 
injured. 

Defenders  of  the  classical  view,  Dejerine  in  par- 
ticular, have  replied  by  advancing  fresh  cases  with 
a  lesion  in  Broca's  gyrus  ^^'ith  aphasia  resulting  ; 
they  contend  that  Marie's  '  quadrilateral '  contains 
the  projection  fibres  of  the  third  frontal  convolution, 
which  in  their  view  explains  the  anarthria  ;  and  they 
maintain  that  most  of  the  fifty-seven  cases  of  aphasia 
in  which  Broca's  convolution  was  intact  were 
associated  with  much  defect  in  understanding 
language  spoken  or  written,  and  that  the  lesion  was 
one  of  the  dominant  auditorv  word  centre  in  the 


254        LOCALIZATION    OF    FUNCTION 

temporal  lobe,   without  which  Broca's  convolution 
cannot  work. 

If  it  were  proved  that  in  cases  of  apraxia,  previously 
referred  to,  the  lesion  was  in  the  first  frontal  con- 
volution for  the  legs,  and  in  the  second  frontal  for 
the  arms,  the  location  of  speech  just  in  front  of 
the  motor  centres  for  the  face  and  mouth  would 
receive  strong  support  by  analogy,  but  all  this  is 
still  very  uncertain. 

To  sum  up,  we  may  express  current  opinion  by 
accepting  the  existence  of  a  large  diffuse  centre  in 
the  left  temporoparietal  region  in  which  recognition 
of  spoken  and  written  language  and  '  internal 
speech '  take  place  ;  when  it  is  seriously  damaged 
these  are  all  lost  and  the  inteUigence  is  impaired. 
Whether  there  is  a  special  departure  platform  in 
Broca's  convolution  for  uttering  speech  is  uncertain, 
but  probably  there  is.  Lesions  of  the  projection 
fibres  from  the  cortex  (?  of  Broca's  convolution) 
will  cause  '  anarthria  ',  that  is,  loss  of  external  but 
not  of  internal  speech. 

Practical  deductions  are,  not  to  trust  aphasia  as 
conclusive  locahzing  evidence  of  a  lesion  in  the  left 
third  frontal  gyrus,  but  rather  to  look  to  the  temporal 
region,  especially  if  there  is  any  defective  apprecia- 
tion of  what  is  said  or  written;  patients  with  left 
temporosphenoidal  abscess,  for  instance,  are  usually 
unable  to  name  correctly  objects  shown  them.  More- 
over, we  are  encouraged  to  believe  that  there  is  no 
need  to  fear  that  small  cortical  injuries  inflicted  by 
the  surgeon  will  cause  aphasia  ;  subcortical  injuries 
are  much  more  Hkely  to  do  so,  by  cutting  off 
projection  fibres. 


IX     THE     BRAIN  255 

MISLEADING     LOCALIZING      SIGNS     OF     INTRA- 
CRANIAL    TUMOUR. 

It  is  very  disappointing  when  definite  signs  usually 
regarded  as  of  importance  in  localization  give  colour 
to  a  diagnosis  as  to  the  position  of  a  cerebral  tumour, 
but  on  the  operation  table  nothing  is  found  in  that 
region.  It  is  more  than  disappointing,  because  un- 
successful attempts  to  find  the  tumour  are  more  fatal 
than  actual  removals.  Some  study  therefore  of  the 
physiolog}^  of  the  production  of  misleading  signs  mav 
be  useful. 

The  principal  traps  are  furnished  by  the  follo\\'ing  : 

1.  Cr-\nial  Nerve  Palsies. — Paralysis  of  one  or 
both  sixth  cranial  ner\-es  is  quite  common,  and  bv 
no  means  proves  that  the  nerve  itself  or  its  nucleus  is 
involved  in  the  lesion.  It  has  been  accoimted  for  by 
stretching,  due  to  a  supposed  backward  displacement 
of  the  whole  brain  late  in  the  development  of  a 
growth  ;  the  abducent  ner\-es  run  straight  forwards 
and  are  slender,  so  the  first  sign  of  the  displacement 
is  a  convergent  squint. 

Other  cranial  nen*es,  including  the  third,  fifth, 
seventh,  and  eighth,  are  occasionally  affected  b\'  dis- 
placements of  the  brain  or  by  pressure. 

2.  Localized  or  General  Convulsions. — Mis- 
takes are  particularly  apt  to  arise  if  the  fit  starts  in 
some  definite  area,  follows  a  slow  and  orderly  march 
to  other  areas,  and  perhaps  affects  only  one  side, 
consciousness  being  lost  late  if  at  all  {Jacksonian 
epilepsy).  It  must,  however,  be  remembered  that 
all   this   may   occur   \Wthout   anv   obvious   cortical 


256        LOCALIZATION    OF    FUNCTION 

lesion  ;    indeed,   the  commonest  cause  of  a  localized 
convulsion  is  ordinary  idiopathic  epilepsy. 

Again,  localized  or  general  convulsions  may  give  a 
wrong  impression  when  arising  late  in  the  course  of 
an  intracranial  tumour  or  abscess,  especially  if  it 
presses  on  the  ventricular  sj-stem  of  the  brain  and 
dams  back  the  cerebrospinal  fluid,  causing  hydro- 
cephalus. The  accumulation  of  fluid  in  one  or  both 
lateral  ventricles  stretches  the  overlying  cortex,  and 
may  give  rise  to  fits,  sometimes  of  a  Jacksonian 
type. 

3.  Bilateral  Spastic  Paresis.- — In  many  cases  a 
hint  is  given  of  the  true  nature  of  these  seizures  by 
the  presence  of  a  shght  degree  of  bilateral  spastic 
paresis,  with  clumsiness  of  movement,  exaggerated 
reflexes,  extensor  plantar  response,  and  a  httle 
rigidity. 

Of  course,  if  this  should  chance  to  be  associated 
with  paratysis  of  a  cranial  nerve,  such  as  the  sixth, 
the  temptation  to  diagnose  a  lesion  of  the  pons  would 
be  very  great.  Fortunately,  this  would  not  be  of 
much  surgical  importance,  as  the  pons  is  not  an 
accessible  structure.  Pontine  tumours  are  often 
unilateral,  and  optic  neuritis  is  usually  absent  ; 
whereas  in  the  class  of  cases  we  are  now  considering, 
optic  neuritis  is  marked  and  old-standing,  and  there 
is  a  long  history  of  headache,  vomiting,  or  other  signs, 
previous  to  the  development  of  spasticity  or  cranial 
nerv^e  palsy. 

In  other  cases,  misleading  locahzing  signs  may 
arise  from  patches  of  secondary  thrombosis,  spreading 
oedema,  or  meningitis  ;  but  none  of  these  is  common. 


IN    THE    BRAIN  257 

The  suspicious  feature  about  all  the  signs  here 
mentioned  is  their  late  development.  Localizing 
symptoms  appearing  when  headache,  vomiting,  optic 
neuritis,  or  other  evidences  have  been  present  for 
months  or  years  are  httle  to  be  trusted.  Early 
localizing  signs,  on  the  other  hand,  are  trustworthy 
in  the  main.  There  is  a  condition  called  serous 
meningitis,  specially  affecting  the  cerebellar  region, 
which  may  be  most  misleading.  It  is  apt  to  get 
well  in  time. 

A  few  words  may  be  said  about  the  significance 
of  ataxia.  This  is  of  course  evidence  of  a  lesion  of 
the  cerebellum,  but  it  may  be  seen  in  other  conditions 
also.  Putting  aside  ataxia  due  to  affections  of  the 
labyrinth,  Friedreich's  ataxia,  and  other  general 
nervous  diseases,  it  may  also  be  caused  by  a  tumour 
in  the  neighbourhood  of  the  red  nucleus  in  the 
isthmxus,  or  in  the  pons. 

OPTIC     NEURITIS. 

It  has  long  been  in  doubt  why  optic  neuritis  should 
develop  in  cases  of  cerebral  tumour.  It  has  been 
attributed  to  the  effects  of  chronic  meningitis,  and 
to  over-filling  of  the  third  ventricle,  with  consequent 
pressure  on  the  underlying  optic  chiasma.  It  is 
now  definitely  estabhshed  by  the  experiments  of 
Gushing  and  Bordley,  and  confirmed  by  clinical 
experience,  that  it  is  a  pressure  effect.  The  growth 
of  the  neoplasm  causes  a  great  and  continued  rise 
of  intracranial  pressure  ;  this  tends  to  dam  back 
the  lymph-flow  returning  in  the  sheath  of  the  optic 
nerve.     The  usual  consequence  of  lymphatic  obstruc- 

17 


258         LOCALIZATION     OF     FUNCTION 

tion  is  produced,  namely,  cedematous  swelling  of  the 
area  drained.  So  the  optic  cup  fills  up,  the  disc  is 
obscured  by  transudate,  and  the  vessels  are  buried 
from  view  in  the  oedema  fluid.  x\ll  this  may  be 
exactly  reproduced  by  intracranial  pressure  in  dogs, 
and  when  the  pressure  is  removed,  restitution  to 
normal  takes  place. 

Several  methods  of  raising  the  intracranial  pressure 
were  employed,  the  best  results  being  obtained  by 
the  insertion  of  sponge-tent  material  inside  the 
skull.  SweUing  and  oedema  of  the  disc,  tortuosity 
of  the  veins,  and  over-distention  of  the  lymph- 
sheath  around  the  optic  nerve  were  all  marked. 
ReUef  of  the  pressure  rapidly  cured  them. 

.\lthough  we  use  the  conventional  term  '  neuritis  \ 
the  histological  changes  are  not  those  of  inflammation. 
For  instance,  there  is  no  arterial  hyperaemia,  and 
the  principal  infiltration  is  ^rith  cells  of  connective- 
tissue  origin,  not  leucocytes. 

Further,  it  has  been  stated  by  many  obser\''ers, 
and  recently  defended,  \\ith  all  his  great  authority 
and  experience,  by  Sir  Victor  Horsley,  that  the  degree 
of  the  neuritis  in  the  two  eyes  is  a  most  reliable 
guide  as  to  the  side  of  the  tumour.  It  is  not  so  much 
the  amount  of  swelling  that  is  to  be  taken  into 
account  as  the  age  and  extent  of  the  changes.  These 
nearly  always  commence  at  the  upper  nasal  quadrant 
of  the  disc.  Thus,  optic  neuritis  best  marked  in  the 
right  eye  is  of  great  value  in  pointing  to  a  right-sided 
tumour.  The  further  forward  the  tumcur,  the  more 
constant  does  this  rule  become. 

It  is  well  known  that  even  if  a  cerebral  tumour 


IX     THE     BRAIN  259 

cannot  be  localized,  palliative  trephining  should  be 
performed  to  relieve  headache  and  save  the  sight. 
If  this  is  undertaken  early,  the  optic  neuritis  passes 
off.  As  the  tentorium  transmits  pressure  badly, 
the  trephining  should  be  in  the  temporal  region  for 
supratentorial  tumours,  and  in  the  occipital  region 
for  cerebellar  tumours. 

Another  valuable  observation  which  we  owe  to 
Gushing  is  that  raised  intracranial  pressure,  par- 
ticularly by  cerebral  tumour,  induces  a  considerable 
limitation  of  the  field  of  vision  for  blue  ;  indeed, 
there  may  be  actual  blue-blindness. 

THE    CEREBELLU?A. 

We  have  been  in  urgent  need  of  some  improvement 
in  our  means  of  locaUzing  tumours  and  abscesses 
in  the  cerebellum.  During  a  period  of  ten  years  at 
the  Bristol  Royal  Infirmar}^  there  were  eight  cases 
of  temporosphenoidal  abscess,  all  of  which  were 
successfully  diagnosed,  and  ten  cases  of  cere- 
bellar abscess,  of  which  only  three  were  correctly 
located  ;  in  three  of  these  ten  cases  the  cerebrum 
was  explored  in  vain,  and  in  two  the  lateral  sinus 
was  thought  to  be  the  cause  of  the  s\TTiptoms.  It 
remains  to  be  seen  how  far  the  fresh  light  recently 
thro\sTi  on  the  subject  and  herein  set  forth  will 
help  us  to  obtain  materially  better  results. 

Sir  Victor  Horsley  and  R.  H.  Clarke  have 
re\'ised  our  knowledge  of  the  functions  and  relation- 
ships of  the  cerebellimi  by  an  ingenious  method. 
Reconstructions  of  a  monkey's  head  have  been  made 
by  cutting  frozen  sections  and  then  piecing  them 


260        LOCALIZATION    OF    FUNCTION 

together  again  ;  by  this  means  it  was  possible  to 
build  a  frame  of  metal  to  fit  about  the  head  of  a 
living  monkey,  carrying  an  insulated  needle  which 
could  be  thrust  through  a  small  trephine  hole  into 
any  desired  portion  of  the  cerebellum,  its  cortex, 
or  its  deep  nuclei  (roof  nuclei),  the  exact  position  of 
the  point  of  the  needle  having  been  determined  by 
a  study  of  the  head  reconstructed  from  the  frozen 
sections.  By  this  means  various  parts  could  be 
stimulated  electrically  without  doing  any  but  the 
slightest  damage  to  the  overlying  structures  ;  more- 
over, by  passing  in  a  strong  current  and  using  a 
double  needle  shielded  nearly  to  the  points,  small 
electrolytic  lesions  either  of  the  cortex  or  of  the 
roof  nuclei  could  be  made,  and  the  resulting 
degenerations  studied  by  suitable  staining  some 
weeks  afterwards. 

The  general  result  was  to  prove  that  the  cortex 
cerebelli  is  a  receiving  platform,  and  that  its  axons 
merely  pass  to  the  roof  nuclei,  from  which  the  efferent 
tracts  start.  Stimulation  of  the  cerebellar  cortex  by 
ordinary  currents  produces  no  obvious  response ; 
stimulation  of  the  roof  nuclei  causes  movements  of 
the  eyes  and  sometimes  of  the  limbs.  We  see  here 
the  reason  why  laterally  situated  tumours  or  abscesses 
lie  so  quiet. 

The  classic  signs  of  a  lesion  of  the  cerebellum, 
determined  both  by  physiologists  and  by  clinicians, 
are  the  following  :  —  (i)  Ataxia  ;  (2)  Atonia  ; 
(3)  Asthenia  ;  (4)  Tremor  :  these  all  affect  the  same 
side  as  the  lesion  ;    (5)  Nystagmus  ;    (6)  Vertigo. 

I.  Ataxia. — This,  one  of  the  most  constant  signs. 


IN    THE    BRAIN  261 

is  easily  detected  if  the  patient  is  able  to  walk. 
When  he  is  in  bed,  it  may  be  brought  out  by  making 
him  try  to  pronate  and  supinate  rapidly  for  a  minute 
or  two  ;  or  to  make  and  unmake  a  fist  quickly,  over 
and  over  again.  This  sign  (adiadochokinesis)  is  the 
more  convincing  if  it  is  unilateral. 

2.  Atonia  is  very  variable  ;  the  knee-jerks  may 
be  absent,  normal,  or  excessive,  and  may  change 
day  by  day.  It  depends  on  the  degree  of  inter- 
ference with  the  reflex  path  for  muscular  tone, 
described  in  the  previous  chapter. 

3.  Asthenia  may  be  evidenced  by  weakening  of  the 
grip,  tendency  to  fall,  or  drooping  of  the  head  on  the 
affected  side.     It  is  not  very  constant. 

4.  Tremor  is  only  occasionally  in  evidence. 

5.  Nystagmus. — These  curious  jerkings  of  the  eyes 
are  of  considerable  importance  in  the  diagnosis  of 
cerebellar  affections,  because,  although  seen  in  such 
conditions  as  disseminated  sclerosis,  they  are  very 
unusual  with  locaUzed  intracranial  tumours.  Un- 
fortunately they  are  not  constantly  present  even 
when  the  lesion  is  in  the  cerebellum,  and,  on  the 
other  hand,  are  usually  to  be  observed  in  patients 
with  disease  of  the  labyrinth  (vestibule  and  semi- 
circular canals).  Seeing  that  most  cases  of  cerebellar 
abscess  follow  otitis  media,  it  has  been  very  difficult 
to  be  certain,  in  the  past,  whether  any  nystagmus 
in  a  patient  with  a  suppurating  ear  was  due  to  the 
labyrinth,  or  the  cerebellum,  or  both. 

Barany,  of  Vienna,  has  shown  that  it  is  possible 
to  induce  nystagmus  in  a  nonnal  person  by  stimu- 
lating the  labyrinth.     This  may  be  done  either  by 


262        LOCALIZATION     OF     FUNCTION 

rotating  the  patient,  or  by  allowing  hot  or  cold  (not 
tepid)  water  to  trickle  in  as  far  as  the  membrana 
tympani.  Hot  water  in  the  right  ear  causes  a 
nystagmus  in  which  the  eyes  slowly  turn  to  the  left 
and  are  corrected  by  rapid  jerkings  to  the  right  ; 
with  cold  water  the  rapid  jerkings  would  be  to  the 
left. 

If  a  patient  with  a  suppurating  ear  has  nystagmus, 
and  it  is  desired  to  know  whether  this  is  due  to 
affection  of  the  labyrinth  or  of  the  cerebellum,  hot 
or  cold  water  should  be  injected  to  see  if  the  nystagmus 
can  be  reversed  in  direction.  If  it  can,  the  labyrinth 
cannot  be  at  fault  ;   it  must  be  the  cerebellum. 

Again,  a  patient  with  severe  vertigo  following  on 
otitis  media  may  be  suffering  from  lab3'rinthitis  or 
from  cerebellar  abscess.  If  injection  causes  no 
nystagmus,  the  labyrinth  is  destroyed. 

The  signs  of  a  cerebellar  lesion  have  recently  been 
re-investigated  by  Gordon  Holmes,  using  war 
material.  His  observations  confirm  the  above  de- 
scription in  the  main.  He  points  out  that  if  the 
patient  is  asked  to  push  against  resistance,  and 
the  resistance  is  suddenly  removed,  the  cerebellar 
case  will  'follow  through',  but  a  normal  person 
almost  immediately  checks  the  movement  of  his 
arm. 

TUMOURS    IN    THE    CEREBELLOPONTINE 

ANGLE. 

This  is  a  very  common  location  for  cerebellar 
tumours,  and  a  comparatively  favourable  one  for 
surger}^  seeing  that  in  many  instances  the  growth 


IX     THE     BRAIN  268 

is  simple,  and  can  be  enucleated  without  recurrence. 
Unfortunately,  the  operative  mortality  has  been  very 
high,  about  50  per  cent.  .Alien  Starr  finds  in  the 
literature  sLxty-nine  cases  cured  by  removal.  In 
many  of  these  there  was  restoration  to  good,  in  some 
to  perfect,  health.  Diagnosis,  therefore,  becomes 
peculiarly  important. 

In  addition  to  the  signs  mentioned  above,  certain 
nerve-root  s3Tnptom5  may  develop,  and  the  pons  may 
be  pressed  on.     Mental  trouble  is  quite  unusual. 

We  may  classify  the  evidence  as  follows  : — 

1.  General :  headache,  vomiting,  optic  neuritis, 
slow  pulse,  blue-blindness,  perhaps  convulsions. 
The  headache  is  usually  suboccipital,  and  there  may 
be  stiffness  of  the  neck. 

2.  Cerebellar  signs :  staggering,  vertigo,  ataxia, 
weakness,  tremor,  and  perhaps  absent  knee-jerk  ; 
these  may  be  unilateral,  on  the  same  side  as  the 
growth.  Nystagmus.  Cerebellar  symptoms  do  not 
usually  appear  for  about  a  year. 

3.  Neroe-root  symptoms  affecting  the  same  side  : 
pressure  on  the  hfth,  with  corneal  anaesthesia  and 
loss  of  reflex,  and  weakness  of  jaw  muscles  ;  pressure 
on  the  sixth,  with  internal  strabismus  ;  pressure  on 
the  seventh,  with  facial  weakness  ;  pressure  on  the 
eighth,  with  tinnitus,  loss  of  perception  for  upper 
notes  (tested  by  Galton's  whistle),  or  absolute  deaf- 
ness ;  pressure  on  the  ninth,  tenth,  and  eleventh, 
with  dysphagia,  laryngeal  palsy,  cardiac  attacks, 
etc.  ;  pressure  on  the  twelfth,  with  deviation  of 
the  protruded  tongue.  Of  these,  the  facial  and 
auditory  ner\'es  are  most  often  affected,  there  being 


264        LOCALIZATION    OF    FUXCTIOX 

complete  unilateral  deafness  in  most  of  the  cases. 
In  cerebellar  tumours  these  two  nerves  may  be 
interfered  with,  but  not  to  any  considerable  degree. 

It  is  a  very  important  point  that  in  the  cases 
favourable  for  surgery  the  signs  of  involvement  of 
the  eighth  nerve  precede  all  the  other  symptoms. 
There  is  great  lowering  of  irritability  to  Barany's 
tests,  even  if  some  hearing  is  presented. 

4.  Pressure  on  the  pons,  causing  crossed  hemiplegic 
weakness,  ^vith  exaggerated  reflexes  and  extensor 
response. 

The  cases  maj'  live  for  years,  but  there  is  a 
Uabihty  to  sudden  death  by  crowding  of  the  cere- 
bellum down  through  the  foramen  magnum. 

The  symptoms  may  vary  much  from  time  to  time, 
on  account  of  circulatory  changes. 

A  serous  meningitis  of  the  same  region  sometimes 
occurs,  and  may  mimic  the  symptoms  only  too 
accurately. 

Gushing  has  been  able  to  reduce  his  operative 
mortahty  to  20  per  cent  by  better  recognition  of 
the  early  cases  arising  on  the  eighth  nerve,  and  by 
his  procedure  of  making  a  bilateral  removal  of  the 
occipital  bone. 

THE     CEREBROSPINAL     FLUID. 

This  fluid  is  clear,  watery,  and  of  low  specific 
gravity  ;  it  contains  almost  no  albumin,  but  some 
sugar.  Until  recently  this  reducing  substance  was 
thought  to  be  a  pyrocatechin  body.  It  contains  no 
cells  in  health,  nor  does  it  contain  the  antitoxins, 
opsonins,   or  alexins  which  are  present  in  plasma. 


IN    THE     BRAIN  265 

lymph,  and  most  serous  fluids.  This  explains  the 
great  liability  to  septic  meningitis  after  injuries  to 
or  operations  on  the  central  nen'ous  system.  As 
urotropine  is  excreted  into  the  cerebrospinal  fluid 
when  given  by  the  mouth,  it  may  usefully  be  admin- 
istered to  prevent  septic  complications  such  as  the 
above,  or  following  on  suppurative  otitis  media. 
Some  success  is  claimed  for  this  procedure. 

The  fluid  is  secreted  by  the  choroid  plexus  into  the 
lateral  and  third  ventricles  ;  it  passes  by  the  Sylvian 
aqueduct  into  the  fourth  ventricle,  escapes  by  the 
foramina  in  the  roof  into  the  subarachnoid  space, 
and  is  absorbed,  partly  by  the  aid  of  the  Pacchionian 
bodies,  into  the  superior  longitudinal  sinus  and  other 
veins.  Hydrocephalus  is  produced  by  blocking  of 
the  foramina  in  the  roof  of  the  fourth  ventricle.  If 
an  exit  is  provided,  large  quantities  of  cerebrospinal 
fluid  may  be  lost  daily. 

Lumbar  puncture  is  a  ver\'  valuable  aid  to  dia- 
gnosis in  various  forms  of  meningitis,  parasj-phihtic 
affections,  etc.,  and  the  fluid  may  be  blood-stained 
after  cerebral  haemorrhage  or  inju^,^  It  is  also 
valuable  in  treatment  as  a  means  of  reducing  intra- 
spinal and  intracranial  pressure,  particularly  if  the 
trouble  hes  below  the  tentorium. 

REFERENCES. 

Gushing  and  Bordley. — "  Observations  on  Experimentally 
Induced  Choked  Disc  ",  Bulletin  Johns  Hopkins  Hospital, 

1909,  XX,  p.  95. 

HoRSLEY. — "  Optic    Neuritis ",     British     Medical    Journal, 

1910.  i.  p.  553. 

HoRSLEY  AND  Clarke. — "  The  Structure  and  Functions  of 
the  Cerebellum",  Brain,  1908,  xxxi,  p.  45. 


266  LOCALIZATION  OP  FUNCTION  IN  BRAIN 

Thiele. — "  The  Optic  Thalamus  and  Deiters'  Nucleus  ", 
Jour,  of  Physiology,  1905,  xxxii,  p.  358. 

Allen  Starr. — "  Tumours  of  the  Acoustic  Nerve  ",  Amer. 
Journ.  of  Medical  Sciences,   1910,  cxxxix,  p.  551. 

Bergmark. — "  Cerebral  Monoplegia  ",  Brain,  1909,  xxxii, 
P-   342. 

Gushing. — "  A  Note  on  Faradic  Stimulation  of  the  Post- 
central Gyrus  in  Conscious  Patients  ",  Brain,  1909, 
xxxii,  p.  44. 

WiLSON.^ — "  A    Contribution    to    the    Study    of    Apraxia " 

Brain,  1908,  xxxi,  p.  164. 
Collier. — "  Recent  Work  on  Aphasia  ",   Brain,  1908,  xxxi, 

P-  523- 
Collier. — "  The    False    Localizing    Signs    of    Intracranial 

Tumour  ",  Brain,   1904,  xxvii,  p.  490. 
Head  and  G.  Holmes. — "  Researches  as  to  Sensory  Disturb- 
ances from  Cerebral  Lesions  ",    Lancet,    1912,  i,   pp.   i, 

79,   144- 
Head. — "  Sensation     and     the     Cerebral     Cortex  ",   Brain, 

1918,  xh,  p.   57. 
Holmes  and  Lister. — Brain,  1916,  xl,  p.  34, 
Holmes. — Brit.    Jour.     Ophthalmology,     191 8,     July,     353  ; 

Sept.,  p.  449. 
Sherrington  and  Leyton. — Jour,  of  Experini.  Physiol.,  191 7. 


267 


CHAPTER     XIV. 

THE    ACTION     OF    CUTANEOUS 
ANESTHETICS. 

DRUGS     APPLIED    TO    THE     UNBROKEN     SKIN. 

IT  has  been  customary  to  relieve  abdominal  pain 
by  the  application  of  hot  fomentations  containing 
opium,  to  treat  sprains  and  bruises  with  lead  and 
opium,  and  to  smear  on  glycerin  of  belladonna  for 
the  discomfort  of  white  leg.  Wliat  dyspeptic  old 
lady  has  not  worn  a  belladonna  plaster  over  her 
heart,  and  what  practitioner  has  not  prescribed  a 
belladonna  liniment  for  vague  aches  and  pains  ? 
The  rationale  of  the  treatment  has  been  that  bella- 
donna, opium,  and  menthol  are  alleged  local 
anaesthetics,  and  it  is  further  supposed  that  they  are 
absorbed  by  the  unbroken  skin.  The  truth  is  that 
they  are  iwt  local  anaesthetics,  and  that  they  are 
scarcely  if  at  all  absorbed  through  the  unbroken 
skin.  Neither  aconite,  cocaine,  carbolic  acid,  bella- 
donna, nor  opium  has  any  power  to  reheve  pain 
when  apphed  to  normal,  healthy  skin. 

It  has  been  well  said  that  "  You  have  not  proved  a 
lie  to  be  a  he,  until  you  have  shown  how  it  came  to 
be  believed".  This  is  very  true  in  science,  and 
especially  in  medical  science.  The  use  of  belladonna 
and  opium   to   relieve   local   pain   was   an   ob\dous 


268  THE     ACTION     OF 

deduction  from  their  great  power,  when  given  by  the 
mouth,  to  relieve  general  pain  by  inducing  sleep  or 
allaying  coUcky  contractions.  In  the  case  of  bella- 
donna and  its  alkaloid  atropine,  the  fallacy  was  the 
more  natural  in  that  they  have  a  genuine  effect 
in  paralyzing  ner\-e-endings,  but,  unfortunately,  it  is 
only  the  efferent  nerve-endings  in  glands  and  unstriped 
muscle  that  are  paralyzed,  not  the  sensory  twigs  in 
the  skin. 

The  fallacy  has  been  maintained  by  the  practice  of 
combining  these  drugs  with  other  and  more  potent 
treatment  ;  thus,  belladonna  is  given  with  counter- 
irritants  such  as  camphor  or  alcohol  ;  warmth  may 
be  appUed  \\dth  the  opium  ;  friction  helps  the  bella- 
donna liniment  to  keep  its  reputation,  and  even  the 
support  of  the  strapping,  with  counter-irritants  in 
it,  assists  the  patient  to  beheve  in  the  value  of  a 
belladonna  plaster. 

We  may  go  one  step  further,  and  say  that  the 
application  of  opium  and  belladonna  to  mucous 
membranes  is  equally  futile.  There  is  no  evidence 
that  opium  suppositories  after  the  operation  for 
piles,  or  laudanum  dropped  into  aching  ears,  have 
any  direct  local  effect.  Of  course,  morphia  may  be 
absorbed  from  the  suppository,  but  in  that  case  it 
presents  no  advantage  over  a  dose  given  by  mouth 
or  hypodermicalh',  and  is  less  certain  in  its  action. 

To  sum  up,  there  is  no  drug  in  common  use  capable 
of  acting  as  an  anaesthetic  on  the  unbroken  skin, 
except  ether  and  ethyl  chloride,  which  freeze  it,  and 
the  only  drugs  which  relieve  deep-seated  pain  when 
painted  on  or  rubbed  into  the  skin  are  the  counter- 
irritants. 


CUTANEOUS     ANESTHETICS  269 

Full  details  of  the  experimental  data  for  these 
conclusions,  which  are  accepted  by  the  leading 
pharmacologists,  will  be  found  elsewhere.  Briefly, 
the  methods  adopted  were  as  follows. 

Strong,  even  dangerously  strong,  solutions  and 
ointments  containing  opium,  atropine  or  belladonna, 
aconite,  cocaine,  carboUc  acid,  and  menthol  were 
rubbed  into  the  skin  of  the  finger,  and  on  the  tongue, 
and  these  were  then  examined  to  see  if  their  sensi- 
bility was  in  any  way  altered.  The  methods  of 
examining  the  skin  of  the  finger  were  as  follows. 
Each  test  was  applied  on  more  than  one  observer 
and  after  varying  intervals  of  time. 

1.  The  Intolerable  Temperature  Test. — For  each 
observer  there  was  a  certain  constant  temperature 
which  was  just  not  intolerably  hot  when  the  finger 
was  dipped  into  warm  water  for  half  a  minute. 
This  was  determined  before  and  after  applying  the 
drug  under  consideration. 

2.  The  Faradic  Pain  Test. — The  strength  of  current 
was  determined,  before  and  after  the  application  of 
each  drug,  at  which  the  damp  finger  first  found 
electrical  stimulation  by  means  of  electrodes  led 
off  from  a  faradic  coil  actually  painful,  the  current 
used  being  small  at  first  and  gradually  augmented. 

3.  Thermal  Discrimination  Test. — We  found  that 
we  were  able,  by  immersing  the  finger  first  in  one 
beaker  of  warm  water  and  then  in  another,  to  detect 
a  difference  in  temperature  of  not  less  than  one  degree. 
This  was  tested  before  and  after  the  apphcation  of 
each  drug. 

4.  General  Testing  by  means  of  a  pin  point,  the 


270  THE    ACTION    OF 

sesthesiometer,  a  wool  pencil,  etc.,  was  also  used. 
In  testing  the  sensibility  of  the  tongue,  we  used  the 
faradic  pain  test  as  described  above  ;  we  examined 
thermal  discrimination  by  applying  warm  metal 
points  at  various  temperatures  ;  we  used  the  aesthesio- 
meter,  and  studied  the  effect  of  the  drugs  on  taste. 

Judged  by  these  standards,  the  various  drugs  fared 
as  follows  : — 

Opium. — -A  5  per  cent  solution  of  morphine 
tartrate  in  water  had  no  effect  on  skin  or  tongue. 

Belladonna. — Very  strong  liniments  had  no  aucES- 
thetic  effect.  Indeed,  if  they  had,  the  drug  could 
be  used  instead  of  cocaine  for  eye  surgery.  The  only 
sign  we  could  obtain  was  diminution  of  sweating 
over  the  skin  area  treated.  There  was  no  flushing 
or  blanching  of  the  skin  or  mucous  membrane. 

Aconite. — Neither  the  B.P.  liniment  nor  ointment 
had  any  effect  on  the  skin.  Solutions  produced 
tinghng  of  the  tongue,  but  we  were  not  quite  confident 
whether  there  was  or  was  not  a  little  reduction  in 
sensibility. 

Cocaitie. — Strong  ointments  and  alcohohc  solutions 
had  no  effect  on  the  unbroken  skin.  Of  course,  if 
the  skin  is  damaged,  the  effect  is  marked.  A  lo  per 
cent  solution  appHed  to  the  tongue  produced  con- 
siderable reduction  of  sensibility,  by  all  our  tests. 

Menthol  produces  a  curious  stimulation  of  the 
nerve-endings  which  detect  cold,  as  is  weU  known. 
A  discussion  of  its  other  actions  would  lead  us  too 
far,  but  any  anaesthetic  effect  is  purely  that  of  a 
counter-irritant. 

Carbolic  Acid  rather  increases  the  sensitiveness  of 


CUTANEOUS     ANESTHETICS  271 

the  finger  to  painful  stimuli.  Its  undoubted  value 
in  relieving  toothache  is  due  to  its  caustic  action  in 
destroying  irritated  nerve-endings.  The  numb  feel- 
ing we  get  after  prolonged  soaking  in  i  in  20  carbolic 
is  due  to  the  formation  of  a  thin  coating  of  killed 
epidermis  over  the  hands. 

The  fact  that  even  cocaine,  which  is  thoroughly 
proved  to  paralyze  sensory  nerves,  fails  to  produce 
the  slightest  effect  when  a  10  per  cent  solution  in 
alcohol,  or  a  10  per  cent  ointment  made  with  lanolin, 
is  rubbed  into  the  skin,  is  strong  evidence  that  little 
if  any  of  these  alkaloids  reaches  the  nerve-endings 
at  all.  Atropine  finds  its  way  into  the  sweat  ducts 
sufficiently  to  reduce  but  not  to  abolish  sweating 
by  its  action  on  the  sweat  glands.  It  is  true  that 
cases  of  poisoning  from  the  application  of  belladonna 
to  the  skin  are  recorded,  but  only  where  there  were 
abrasions  or  sores  present,  or  perhaps  in  young 
children  whose  skin  is  very  delicate. 

It  may  be  objected  that  there  is  sufficient  clinical 
eWdence  of  benefit  from  these  drugs  to  defy  negative 
results  by  experimental  methods,  but  any  who  claim 
this  must  not  confuse  the  issue  by  combining  the 
belladonna  or  opium  with  camphor,  heat,  rest,  or 
strapping.  Again,  it  may  be  suggested  that  atropine, 
at  least,  has  some  vasomotor  effect,  but  we  failed 
to  observe  any,  and  indeed  we  doubt  if  it  ever  reaches 
the  blood-vessels  when  rubbed  into  the  unbroken  skin. 

It  is  a  thankless  task  to  pull  down  strongholds  ot 
belief,  but  it  is  necessary,  if  only  to  direct  more 
attention  to  the  true  means  of  giving  relief  to  pain, 
including    general    drug    treatment,    rest,    massage. 


272  ACTION  OF  CUTANEOUS  ANAESTHETICS 

counter-irritation,  heat,  and  passive  hyperaemia. 
Moreover,  a  recognition  of  the  failure  of  drugs  saves 
useless  expense,  and  may  banish  from  patients' 
houses  some  of  the  commonest  of  powerful  poisons. 
Belladonna  liniment,  for  instance,  has  been  respon- 
sible for  an  immense  number  of  alarms,  illnesses, 
and  even  fatalities. 

REFERENCE. 

A.  Rendle  Short  and  Walter  Salisbury,  British  Medical 
Journal,  1910,  i,  p.  560. 


273 


APPENDIX. 

ABSORPTION    OF     NITROGEN     FROM 
AMINO-ACIDS. 

We  have  made  several  observations  on  patients  '  fed ' 
with  nutrients  of  milk  digested  with  pancreatic  extract  for 
twenty-four  hours  in  an  incubator,  so  as  to  convert  most 
of  the  protein  into  aminoacids.  Such  nutrients  are  not 
irritating.  An  example  of  such  a  case  is  the  following 
(I  am  indebted  to  Mr.  P.  A.  Opie  and  to  Dr.  Bywaters 
for  some  of  the  analyses). 

Case  I. — A.  H.,  age  25,  female,  suffering  from  vomit- 
ing and  gastric  pain,  not  relieved  by  a  diet  of  peptonized 
milk,  was  put  on  nutrient  enemata  as  follows  : — 

March  28-29. — By  mouth  :    water. 

By    rectum  :     saline,    15    ounces    three 
times  a  day. 
March  2g-April  i. — By  mouth  :    water. 

By  rectum  :     6   per   cent  glucose, 
I  pint  three  times  a  day. 
April  1-4. — By  mouth  :    water. 

By  rectum  :    milk  digested  for  twenty-four 
hoars,  six  ounces  every  four  hours. 
April  4. — By  mouth  :    peptonized  milk. 


Urine  in 
ounces 

Ammonia  N 
per  cent 

Daily  output  of 

N  in  urine 
in  grams. 

March  28-29 
29-30 

29 
22 

3-2 

8-03) 

628    Av. 

30-31 
,,         31-April  I* 
April  1-2 
„       2-3 
»       3-4 

26 
26 
16 

22 
32 

0-8 

12-3 

127 

12-5 

9-3 

4-36     604 
5-56 

!t?)Av. 

^■^    f770 
9-53]  ^  ^ 

•,       4-5 

31 

0-5 

9-02 

•Glu 

cose  not  wel 

1  retained. 

18 


274 


APPENDIX 


It  will  be  observed  that  instead  of  showing  the  usual 
steady  fall,  the  nitrogen  output  is  increased  during  the 
three  days  of  feeding  on  aminoacids. 

Case  II. — This  patient,  a  man,  was  fed  as  follows, 
the  daily  output  of  nitrogen  in  the  urine  being  also 
shown  : — 


By  mouth 

1 

By -turn    lYrJ" 

Ammonia 
N  per  cent 

Daily  output 

of  N  in  urine 

in  grams 

April 
26-27 

Milk 

1 

Nil               1       21 

1-4 

I4'3 

27-28 

Water 

Saline             19 

2-9 

10-7 

28-29 

Milk  pepto-  \ 
nized   20 
minutes ;      \ 
.3V  6-hourly!) 

3'5 

9-6 

29-30 
30-May   I 

May 
1-2 

>> 

'  Milk  pepto- 
nized  24 
hours,  3V    i 
6-hourly, 
with  3j  of 

\^     glucose 

20 
16 

) 
Vio 

4-8 
2-9 

2-9 

6-8 
7.9 

7-2 

2-3 

»f 

>» 

21 

3.0 

14-4 

3-4 
4-5 

/  Pept. 

milk 

3V  2- 

i  hourly 

(   iMilk 

.       Nil 

15 
23 

3'7 

2-8 

II-2 
161 

) 

5-6 

-,  3  VI J  2- 
(  hourly 

[ 

54 

0-9 

13-7 

As  the  accompanying  chart  shows,  the  absorption  and 
output  of  nitrogen  are  very  considerably  increased  when 
the  milk  has  been  digested  with  pancreatic  extract  for 
twenty-four  hours.  The  increased  absorption,  as  usual, 
does  not  increase  the  output  for  about  twenty-four 
hours. 


APPENDIX 


275 


a  17 

<  15 
gl4 
z  13 

o  10 
a: 
H    9 

^   8 

O    7 

t   5 

§^ 

^' 
=!   2 

2  . 

DAY     OF    FAST.               | 

1 

2 

3 

4 

5 

6 

7 

8 

9 

JO 

« 

f 

t 

1 
/ 

\ 

V 

1  \ 

/ 

w 

1 
1 

\  1 

\ 

1 
1 

•^ 

1 

\ 

1 

r 

\ 

I 
/ 

1 

\ 

\  , 

'%: 

■^/ 

1 

\ 

/  ^ 

s/ 

\ 

y 

U 

V 

■ 

m, 

''//M/.: 

;^^^M^^WS^ 

m 

>  Case  II. 


Case  I. 


Case  I. 
Case  II. 

v////y////\  Nutrients  peptonized  20  minutes. 
■■■I  Nutrients  peptonized  Z4- hours- 
^^^/A'j^  Mouth  feeding. 


276 


INDEX 


PAGE 

ABDERHALDEX,  serum  dia- 
gnosis of  pregnancy       . .     lol 
Abdominal  injury  and  shock      82,  86 

—  operations,  intestinal  paraly- 

sis after,  treatment  . .     118 

physostrgmine  after       ..     117 

value  of  novocain  . .     103 

Abel,  red  corpuscles  in  Locke's 

fluid  for  transfusion  . .  21 
Abscess  of  brain  248,  254,  256,  259 
Absorption   in   gastro-intestinal 

tract         131 

Achromatic  spindle  . .  . ,  148 
Achsner  on  pituitary  gland  . .  188 
Acidosis  or  acetonaemia  . .     205 

—  in  shock         . .  . .  . .       87 

Aconite  as  local  analgesic  . .  270 
Acromegaly         . .  . .        191,  193 

—  operation  on  pituitary  gland 

for  194 

—  viscera  in       . .  . .  . .     192 

Addis  on  haemophilia   . .  36,  37 

Adenoma  of  thyroid     . .  . .     146 

Adiposity  and  pituitary  gland  192, 193 


Adrenalin  dangerous  in  shock 

—  in  osteomalacia 

—  and  ventricular  fibrillation. . 
Adrenalin-chloroform,  fatal  com- 
bination  . . 

Adrenalin-ether  combination  , . 

Agnosia    . . 

Albee,  bone  graft  in  Pott's  disease 

Albtmiinuria 

Albuminuria,  calcium  therapy  in 

Alcohol  harniful  ia  shock 

Alimentary  canal,   sensation  in 

Alkalosis  in  shock  (Moore) 

Alum  in  haemophilia 

Amblyopia  from  iodoform 

Amenorrhoea 

—  and  pituitary  lesions 

—  • — ■  feeding     . . 

—  relation  of  thyroid  gland  145,  146 
Amino-acids  in  shock    . . 
Ammonia-nitrogen  in  shock     . . 
Amputation    at    hip- joint    and 

shocK        . .  . .  8 

Anaemia,  pemiciotis,  haemorrhage 
in  . . 

—  spleen-extract  therapy  in  . . 


100 
146 

205 

204 
205 
249 
163 
31 
43 
100 
121 


..   39 

..  179 

..  194 

146,  192 

145,  195 


87 


38 
26 


PAGE 

Anaesthesia    in    cortical    brain 

lesions      . .  . .  . .     242 

—  Crile's     anoci-association 

method 102 

—  intraspinal,  danger  of  . .        96 

—  spinal,  bad  in  war  . .  . .  102 
Anaesthetic,  choice  of    . .  . .     102 

—  nitrous-oxide-oxygen  best  to 

prevent  shock     . .  . .     102 

Anaesthetics         . .  . .  . .     105 

—  cutaneous,  no  action  on  un- 

broken skin  . .  . .     267 

Anal  canal,  sensation  in  . .     122 

Anaphylaxis  after  operations  on 

hydatid  cysts      . .  . .       42 

—  risks  of  . .  . .  . .       41 

—  symptoms      . .  . .  . .       42 

Anarthria  of  Marie  253,  254 

Aneurysm  and  iodides  178,  180 

—  traumatic,  ossification  in    , .     158 
Anoci-association  anaesthesia  . .     102 
Anterior  horn  diseases  . .  . .     217 

Antipepsin  . .  . .  . .     125 

Antiperistalsis,  surgical  import- 
ance . .  . .  . .     113 

Antiscorbutics     . .  . .  8,  10 

Antithrombin      . .  . .  . .       30 

—  not  in  excess  in  haemophilia      38 
Antitoxic  serums,   risk  of  ana- 
phylaxis . .  . .  . .       42 

Antitoxins  absent  from  cerebro- 
spinal fluid  . .  . .     264 

Aorta,  atheroma  of,  after  thyroid- 
ectomy    . .  . .  . .     171 

Aphasia    . .  . .  . .        250,  251 

—  former  and  recent  views  on  251 
Appendicitis        . .  . .  . .     119 

—  and  chronic  dyspepsia      127,  128 

—  ileal  stasis     . .  . .  . .     115 

—  relation  to  gastric  and  duo- 

denal ulcers         . .  . .     126 

Apraxia    . .  . .  . .  . .     248 

—  corpus  callosum  and  250,  251 
Arctic  expeditions  and  scurvy  8,  9 
Arms,    attitude   in   fracture    of 

cervical  spine     . .  . .     217 

Arteries  and  capillaries,  calibre 

may  vary  independently  84 
in  histamine  poisoning . .       91 

—  contracted  in  shock  83,  84 


INDEX 


277 


PAGE 

Arteriosclerosis  and  iodides 

178,  180,  185 

—  in  myxcedcma           ..          ,.  180 
Astereoijnosis      . .          . .          . .  242 

Asthenia  in  cerebellar  lesions  . .  261 
Asthma  caused  by  foreign  pro- 
tein          . .          . .          . .  42 

Ataxia  in  brain  localization 

1'57,  261,  263 

—  cerebellar  lesions      . .        260,  263 

—  posterior  ner\-e-root  lesions  225 
Atheroma  in  cretin  lambs  . .  180 
Athetosis,  operation  for            . .  242 

—  and  the  optic  thalamus  . .  243 
Atonia  in  cerebellar  lesions  261,  263 
Atropine  in  chloroform  poisoning  204 

—  solutions  apt  to  grow  a  very 

poisonous  mould            . .  204 

Attraction,  chemical,   in  nature  230 

Autolysis  in  shock         . .          . .  90 

Axon,  growth  of  in  embryo     . .  230 

Bacteria,  quantity  in  faeces  . .  132 
Baldwin,  Miss  H.,  formation  of 
oxalates     from     carbo- 
hydrates    199 

Ballance  on  nerve  anastomosis  234 

Banti's  disease   . .          . .          . .  27 

Bdrdny  on  experimental  nystag- 
mus          . .          . .          . ,  261 

Baumann,  iodine  in  thyroid     ..  172 
Bayliss's  gum-saline  solution  ..  101 
Beans,    germinating,     antiscor- 
butic vitamines  in         . .  10 
Bederc  on  exophthalmos           . .  172 
Bedford  on  suprarenal  theory  of 

shock        . .          . .          . .  92 

Beef,  time  remaining  in  stomach  110 

Beer  and  scurvy             . .          . .  lo 

Bell,  Blair,  on  pituitary  gland 

188,  189,  194 

Belladonna  as  local  analgesic  . .  270 

—  and  milk  secretion   . .          . .  147 

—  poisoning  from  local  applica- 

tions        . .          . .          , .  271 

—  and  sweat  glands  . .  . .  271 
Benzol,  effect  on  blood . .  . ,  32 
Bergmark  on  flaccid  paralysis..  247 

—  on     lesions     of     postcentral 

gyrus        242 

—  on  motor  reflex  arc  . .  . .  209 
Beri-beri  . .         . .         . .         . ,  3 

—  asylum           . .          . ,          . .  4 

—  and  husked  rice        . .          . .  4 

—  in  Malay  States        , .          . .  4 

—  '  wet '  form    . .          . .          . ,  5 
Berkeley,  Glos.,  goitre  well  at  . .  178 
Betz  cells,  Limitation  to  ascend- 
ing frontal  convolution. .  246 

Bircher  on  goitre  in  rats            . .  178 


PACK 

Bireher  on  goitre  wells  . .         . .  177 

Bladder  in  spinal  cord  injury  . .  224 
Bland-SuUon  on  rickets  at  the 

London  Zoo        . .          . .  11 

Blindness  and  pituitary  tumour  192 
Blood,  calcium  salts  and         43,  170 

—  coagulation  of           . .          . .  28 

causes  of  delay  . .          . .  35 

results  of  deficient          . .  31 

time,     coagulimeter      . .  30 

effect  of  bleeding  on  35 

—  corpuscles,  function  of  liver 

and  spleen  in  relation  to  25 

formation   of   microcytes 

and  poilkiJocytes  from  . .  25 

—  in  shock         . .          . .          . .  87 

—  diseases  and  the  spleen       . .  26 

—  donor,  restoration  of  blood- 

volume  of            . .          . .  87 

—  effect  of  benzol  on  . .          . .  32 

—  estimation  of  volume           . .  17 

—  fat  in  (McKibben,  Short)  . .  93 

—  in  liaemophilia           . .          . ,  33 

—  platelets         . .          . .          . .  32 

—  pressure  and  curare. .          . ,  96 
dangerous  fall  with  intra- 
spinal anaesthesia       . .  96 

and  depressor  fibres      . .  62 

high,  pulsus  alternans  in  78 

and  pituitary  extract    . ,  190 

result  of  lowered            . .  98 

in  shock  . .  . .  82,  86 

— •  in  purpura  haemorrhagica  . .  32 

—  restoration     after    haemor- 

rhage . .        . .  16,  87 

—  red-cell     increase     in     high 

altitudes  . .          . .          . .  176 

—  researches  on            . .         . .  16 

—  scorching    and    shock    after 

bums        . .          . .          . .  82 

—  serum  proteids,  restoration  of  18 

—  transfusion     . .          . .          , .  19 
animal's  blood  toxic  to 

man      ..          ..          ..  19 

effect  of  citrated  blood. .  20 

fate  of  red  corpuscles    . .  25 

four  blood  groups           . .  23 

for  haemophilia  . .  20,  41 

for  haemorrhage..          ..  19 

incompatibility  and       , .  22 

for  pernicious  anaemia  . .  20 

risks  and  dangers  of     . .  22 

in  shock              . .          20,  102 

contracted  veins  may 

cause  diflficulty  17,  83 

test  for  blood  groups      . .  24 

by  means  of  red  corpuscles 

in  Locke's  fluid  . .          . .  21 

—  volume  after  severe  haemor- 

rhage     , 18 


278 


INDEX 


PAGE 

Biood  volume,  fall  in  shock-hsB- 

moixhage         . .          . .  86 

as  a  guide  to  prognosis  ia 

shock    . .          . .          . .  86 

in  obesity           . .          . .  18 

pregnancy            . .          • .  18 

reduced  in  shock           . .  85 

vital-red  estimation       . .  86 

Boeke  on  end-plates       . .          • .  210 
Bone-grafting  (see  Bone  Growth) 

Bone  growth     . .          . .          . .  lo2 

blood-clot  and     . .          . .  152 

callus  and            . .          . .  155 

in  animals     . .          . .  161 

excessive        . .          . .  160 

cambium  layer  . .          . .  161 

chips  in  omentum          . .  158 

continual  change             . .  156 

and  ductless  glands       . .  165 

effect  of  tongue  on  jaw. .  156 

toxins    and    internal 

secretions. .          . .  156 

epiphyses             . .          . .  153 

after  excision  of  elbow  . .  157 

exostoses              . .          . .  161 

■  factors     inducing     bone- 
corpuscles  to  proliferate  159 

from  fragments  . .          . .  158 

in  girth    . .          . .          . .  154 

grafting    . .          . .          . .  163 

—  —  —  factors  concerned  in  164 

fate  of  grafts             . .  164 

relation  of  osteoblasts  164 

periosteum  to     . .  164 

of  rib-cartilage         . .  165 

Haversian  canals            . .  155 

Hey  Groves  on  . .          . .  159 

Hunter's  experiment     . .  153 

interstitial  changes        . .  156 

in  length  . .          . .          . .  153 

Macewen  on        . .          . .  153 

madder  experiment        . .  154 

• massage     after    fracture 

causing             . .          . .  160 

myositis  ossificans  and  160,  161 

osteoblasts  and  . .          . .  152 

periostitis  and     . .          . .  161 

periosteum  in  relation  to 

153,  154,  155,  156 

—  —  recent  research  on       152,  155 

regeneration  of  bone     . .  155 

apart  from  periosteum  157 

—  —  —  from  periosteum     161,  163 

in  subperiosteal  fractures  159 

surgical    apphcation     of, 

researches  on      . .  . .     159 

Bowel  manipulation  arrests  peri- 
stalsis      . .  . .  . .     117 

Boyd  and  Robertson,   on  rectal 

feeding 133 


PAGB 

Brain,     abscess     in     Eolandic 

area           248 

—  American  crowbar  case       . .  247 

—  calcarine  area  and  vision    . .  238 

—  concussion  and  shock          . .  81 

—  function  of  optic  thalamus  243 

—  internal  capsule  in  man  and 

monkeys               . .          . .  246 
and  rigidity  . .          . .  247 

—  localization    . .          . .          . .  237 

of  aphasia            . .          . .  251 

apraxia     . .          . .          . .  248 

ataxia       . .          . .          . .  257 

cerebellar  lesions            . .  259 

■  Holmes'  test       . .  262 

cerebellopontine  tumours  262 

and  convulsions  . .          . .  255 

of  cortical  lesions  237-254 

cranial  nerve  palsies   255,  263 

early  and  late  developed 

signs      . .          , .          . .  257 

frontal  cortex     . .          . .  245 

of  function           . .          . .  237 

Head's  observations       . .  242 

of  hearing            . .          . .  239 

Horsley's  apparatus       . .  259 

macula     . .          . .        238,  239 

motor  initiating  centre . .  250 

of  pain  and  pleasure       . .  243 

in  right-handed  people..  250 

of   sensation         237,  240,  245 

sense  of  space     . .          . .  245 

Sherrington  and  Leyton's 

recent  work     . .          . .  246 

'  silent  area  '       . .          . .  247 

of  speech  functions  (Marie)  253 

tumours   . .           246,  259,  262 

vision       . .          . .          . .  237 

—  meningitis      . .          . .          .  •  256 

—  primitive  sensory  cortex  of  243 

—  results  of  cortical  lesion      . .  210 
internal  capsule  lesion..  210 

—  sensory  cortex          ..          ..  2-14 

—  and  spinal  shock      . .          . .  95 

—  tumour  of 

250,  255,  257,  259,  262,  264 

and  colour  vision            . .  269 

Breasts,  pain  in,  from  deficient 
thyroid  secretion 

—  ovary,  effects  of 
'  Brittle  man  '     . . 
Brown,  Graham,  on  laughter  in 

apes 
on  motor  path    . . 

—  on     tetany     after    thyroid- 

ectomy 
Brown-Scqnard    and    testicular 

extract     . .  . . 

BurckharVs  cases  of  aphasia 


Burdach,  columns  of 


146 
140 
161 

245 
209 

183 

144 

..     252 

212,  213 


INDEX 


279 


PAGE 
Burrow  and'Cartcr''on  recovery- 
tune  of  injured  nerves  . .  232 

Cabbage  as  antiscorbutic         . .  10 

'  Cachexia  strumipriva  *            . .  KifJ 

Ctacoplioation      ..          ..          ..  120 

CsBCum,     ell'wt    of    acids     and 

alkalies  on           . .          , .  116 

Calcium  in  blood           ..          ..  170 

—  chloride  before  operations^in 

jaundice  . .          . .        '. .  38 
for  tetany            . .          . .  170 

—  and  magnesium  salts,  relative 

value  of    . .          . .          . .  44 

—  metabolism  and  tetany    170,  171 

—  no  effect  on  rickets  . .          . .  13 

—  salts  and  blood  coagulation  29 

effect  on  ovary  . .          . .  43 

parathyroids             . .  43 

in  haemophilia     . .          . .  36 

for  htemophilic  bleeding  40 

and  menstruation          . .  138 

and  menopause  . .          .  •  142 

reverse  action  of            . .  40 

■  therapeutics  of   . .          . .  43 

Calculus,  oxalate            . .          . .  200 

—  uric  acid         . .          . .          . .  200 

—  urinary,  and  x  rays . .  . .  200 
Callus  formation            . .        155,  159 

in  animals           . .          . .  161 

Calories  required  in  food           . .  1 

Camphor  in  shock  . .  . .  100 
Cancer  of  breast,  effect  of  ovary 

on             140 

—  section    of    posterior   nerve- 

roots  for  pain  of . .          ..  227 

Cannon,  blood-count  in  shock. .  85 

—  and  others,  acidosis  in  shock  87 
Capillaries  in  histamine  poisoning  84 

—  in  shock  . .  . .  84,  94 
Carbohydrate  starvation  . .  1 
Carbohydrates,  fermentation  of  199 

—  formation  of  oxalates  from  199 

—  in  stomach    . .          . .          . .  109 

Carbolic  acid  as  local  anaesthetic  270 
Carbon    dioxide   and    intestinal 

movements          . .          . .  112 

for  hnnmophilic  bleeding  40 

Cardia,  '  nodal  tissue  '  sphincter 

of 114 

Carlson  on  hunger  sensation    . .  122 

—  on  pain  in  gastric  and  du- 

odenal ulcer        . .          . .  122 

Case  on  ileocsecal  valve  incom- 
petence   . .         . .         . .  117 

Castration  and  thyroid  depriva- 
tion             167 

Cauda  equina  lesions,  operation  in  224 

tumour,  diagnosis  of     . .  220 

Cell  renewal        . .         . .         . .  147 


PAOB 

Cerebellar     peduncle,     inferior, 

function  of          . .          . .  210 

—  tracts              215 

Cerebellopontine  tumours         . .  262 

Cerebellum,  abscess  of  . .  . .  259 
Cerebrospinal   fluid,   absence  of 

antitoxins,  etc.,  from    . .  264 

composition  of    . .          . .  264 

and  urotroi)ine    . .          . .  265 

Cretinism,  treatment  of             . .  173 

Charcot  joints,  experimental   . .  225 
Chick  and  Hume,  antiscorbutic 
value  of  lemon-juice  and 

of  lime-juice       . .          . .  10 

Chilblains             31 

—  calcium  salts  in  . .  . .  44 
Children,  diet  table  for. .          . .  14 

—  small,  and  pituitary  gland. .  195 
Chittenden  on  food  required  . .  2 
Chloroform  as  anaesthetic         . .  102 

—  poisoning        . .          . .          . .  201 

action  on  medulla          . .  201 

viscera  and  acidosis. .  201 

adrenalin  increases  danger  204 

atropine  in          . .          . .  204 

in  cats 202 

dangers  leading  to         . .  202 

delayed 205 

— ■ and  acidosis  . .          . .  205 

pathology  of             . .  206 

prevention     . .          . .  206 

signs  of          . .          . .  206 

fibrillation  of  ventricle  in 

77,  202 

heart  massage  in           . .  204 

— ■  —  not  due  to  vagus  . .  202 
— •  —  prevention  by  scopolamine  204 

sudden  arrest  of  heart  . .  201 

treatment      . .          . .  203 

Cholera,  hypertonic  saline  solu- 
tion for    . .          . .          . .  103 

Chromosome,    additional,    as    a 
factor  in  the  causation  of 

sex            . .          . .          . .  151 

Chronic  dyspiepsia  and  appendi- 
citis             127 

Citrated  blood,  action  of           . .  20 

Coagulation  time  in  jaundice  . .  38 

Coagulimeter       . .          . .          . .  30 

Cocaine  and  the  skin  . .        267,  271 

Cochlear  nuclei   . .          . .          . .  240 

Cod-liver  oil,  effect  on  teeth    . .  13 

Coffee  in  shock    . .          . .          . .  99 

Cold  in  myxcedema       . .          . .  167 

Colic,  intestinal,  cause  of         . .  118 

Colitis  and  tetany          . .          . .  170 

Colon,  absorption  in     . .          . .  131 

—  not  necessary            . .          . .  132 

Colour   vision   and   intracranial 

tumour    ..  ..        259,  263 


280 


INDEX 


PAGE 

Constipation        . .          . .          . .  118 

Conus  medullaris,  tumour,  dia- 
gnosis of  . .          . .          . .  220 

Corpus  luteum,  function  of      . .  141 

Corpuscles,  nucleated  red         . .  18 

—  red,  fate  of    . .          . .          . .  25 

Cotter,  the  Bristol  giant           . .  191 

Cresyl-blue  in  blood  examination  18 

Cretinism  and  the  thyroid  gland  165 

Crile  method  of  anaesthesia     . .  102 

—  on  morphia  in  shock           . .  99 

—  and  Dolley  on  nerve  cells  in 

shock        88 

Croton  oil  as  purgative. .          . .  118 

Cryptorchism      . .          . .          . ,  142 

—  and  ductless  glands  of  . .  145 
Cuneate  nucleus  ..  ..  213 
Curare  and  blood  pressure  . .  96 
Cushing  on  blue-blindness        . .  259 

—  on  cerebellar  tumour  opera- 

tions            264 

—  on  localization  of  hearing  . .  240 

—  on  pituitary  gland  . .         188,  194 

—  —  operations            . .          . .  194 

—  on  postcentral  convolution  241 

—  and  Bordley  on  optic  neuritis  257 
Cushing' s  giant    . .          . .          . .  191 

Cutler  on  iodoform        . .          . ,  178 


PAGE 
28 


Dale  on  histamine  and  shock  . , 

—  and  Laidlaw  on  histamine  and 

and  shock  . .  91 

Deafness 

De  Buck,  case  of  apraxia 
Deep  sensibility . . 
Deiter's  nucleus . . 
Bejerine  on  aphasia 
Dermatitis  from  iodoform 
Diabetic  acidosis  or  acetonsemia 
Diabetics,  general  antethesia  in 
Diarrhoea 

—  lienteric 

Digitalis    as    a    cause    of   sinus 
arrhythmia 

—  and  fibrillation 

—  in  shock 

Diphtheria   antitoxin   in   haemo- 
philia 

D.T.P.,   or   '  distal  tingling   on 
percussion  ' 

Diuretic,  pituitary  extract  as  . . 

Lixon  on  atropine  in  chloroform 
poisoning 

Dog  and  sugar  feeding  . . 

Dropsy  after  saline  transfusion 

Duhamel,   experiment   on   bone 
growth     . .  . .        154, 

Dukes    and     Short,     ammonia- 
nitrogen  in  shock 

Duodenojejunal  flexure  sphincter 


84 

,  94 
240 
249 
212 
222 
253 
178 
205 
206 
111 
113 

64 

74 
101 

40 


196 

204 
199 
104 

157 


114 


ECK'S  fistula 

Eczema,  test  for  foreign  protein 

as  cause  of 
Edmunds  on  exophthalmos 

—  goitre  in  fowl 

—  parathyroids 

—  tetany 
Egg  albumen,  cause  of  asthma 

and  hay  fever     . . 

—  antineuritic  substance,  in  . . 

—  time  remaining  in  stomach 
Eiselsherg,  von,  on  atheroma  in 

cretin  lambs 

—  on  thyroidectomy  in  animals 
Elbow,  excision  of 
Electrocardiography 
Eloesser  on  trophic  lesions 
Embolism      of      osteoblasts     a 

possible  cause  of  myositis 

ossificans 
Embryology  of  nerves  . . 
Emotional  movements  and  optic 

thalamus 
End-plates,  medullated  and  non- 

meduUated 
Enemata,     nutrient,     chart    of 

nitrogen  output. . 

report  of  cases    . . 

Enophthalmos  as  a  consequence 

of  thyroidectomy 
Epicritic  sense    . . 
Epilepsy,  idiopathic,  as  a  cause 

of  localized  convulsion . . 

—  Jacksonian,  and  brain  locali- 

zation 
Epiphyses,  growth  of    . . 
Erepsin     . . 
Erlanger  and  Gasser,  blood-volume 

in  pure  shock     . . 

gum  and  dextrose  solution 

Ether  as  anaesthetic 
*  Exam.-funk  diarrhoea' 
Exopiithalmic  goitre 

—  • —  cause 

pathology 

practical  deductions 

treatment 

Exophthalmos  in  thyroid  feeding 

168,  172 
Exostoses  . .  . .  . .     161 

Fabre  and  Thevenvt  on  congenital 

goitre        . .          . .          . .  176 

Facial  paralysis  and  optic  thala- 
mus             243 

Faecies,  bacteria  in        . .          . .  132 

Fallopian  tube    . .          . .          . .  139 

Fat  in  blood 93 

stomach               . .         . .  109 

—  effect  on  teeth          . .         . .  13 


43 

172 
175 
169 
183 

43 
5 

110 

180 

171 

1 

52 

225 


161 

230 

243 

210 

275 
273 

167 
212 

255 

255 
153 
133 

86 
101 
102 
111 
181 
181 
181 
184 
184 


INDEX 


281 


PAGE 
6 


6 
205 

206 
191 
128 

39 
31 
30 
29 
29 
36 
31 


14: 


Fat-soluble  A      . . 
Fat-starvation     . . 
Fatfs  aiiimal-derived,  importance 
of 

—  katabolism  of 
Fatty  desreneration  in  delayed 

chloroform  poisoning 
Fatccftt  on  Bristol  eiant 
Fenwick  on  hyperchlorbydria 
Ferric   chloride   in    hemophilic 

blee«iing  . . 
Fibrin 

—  ferment,  a  misnomer 

—  table  showing  formation  of 
Fibrinoeen 

—  in  haemophilia 
Fibrinolysins 
Foetus,  internal  secretion  from, 

as  cause  of  lactation 
Food,  calories  required  in 

—  deficiency  diseases  . . 

and  vitamines 

signs  of    . . 

—  fat  required  in 

—  minimum  nitrocreii  required  in 

—  proteid  require-!  in  . . 

—  reqniremencs  of  man 
foreign   protein  as  a  cause  of 

eczema 

test 

Forssman  on  nerve  regeneration 
Fractores,  disadvantage  of  mas- 
sage and  movements  after 

160,  161 

—  regeneration  after   . .         . .     155 

—  repair  of        . .  . .  . .     159 

—  ununited,  thyroid  feeding  and 

potassium  iodide  for     . . 
Froe,  ovum  development 
Frdhlich     on     pituitary     and 

infantilism 
Frontopontic  and  temporopontic 

tracts  and  muscle  tone . . 
Fruits  and  oxaluria 
Funk,  Casimir,  and  beri-beri  . . 


3   — 


1   — 


43 

43 

231 


165 
149 

192 

210 

200 

4 


Gall-bladder  and    gastric  and 

duodenal  ulcers  . .     126 

Gall-stone   colic   and  arrest   of 

peristalsis  . .  . ,     117 

Gas-gangrene     and     shock-like 

symptoms  . .  . .       90 

'  Gas-pains  *     after     abdominal 

operations  . .  . .     103 

Gastralgia  122 

Gastric  crises,  section  of  posterior 

nerve  roots  for  . .     226 

—  and  duodenal  ulcer,  causes  of 

pain  in      . .  . .  . .     122 

—  ulcer 119 


PAGE 
Gastric'nlcer,  action  of  acid  and 

alkalies     . .  . .  . .     122 

difficulty  of  diagnosis    . .     127 

excision  of  . .  . ,     128 

and  hydrochloric  acid  ..     121 

hyperchlorbydria  . .     125 

Gastrojejunostomy         . .  . ,     128 

—  cause  of  failure         . .         . .     125 

—  digestion  after  . .  . .     130 

—  effect  on  hydrochloric  acid. .     130 

—  physiology  of  . .  . .     129 

'  Gastrostaxis  ' 129 

Genital     atrophy     and     hyi)o- 

pituitism 

—  glands 

—  glands,  control  by  internal 

secretions 
GennarL  white  line  of 
Geseli  on  fall  of  blood-pressure 

and  blood-flow 
Gigantism 

—  operation  on  pituitary  for 
Gland,  pineal 

overgrowth  of 

—  pituitary 
and  pineal 
sterility    and    impotence 

associated  with 

—  suprarenal,  enlargement 

—  thyroid 

and  amenorrhoea 

Glands,    ductless,    before    and 

after  puberty 

methods  of  study 

Glans  penis,  protopathic  sense 
dey  on  parathyroids 
Glucose,  deficient,  effect  of 
Glycosuria  and  pituitarr  gland 

"189,  192,  193 

—  sympathetic  system 

—  vagi    . . 

Goitre,  exophthalmic  (see  Exoph- 
thalmic Goitre) 

(joitre  (see  also  Thyroid) 

—  on  (Captain  Cook's  voyage . . 

—  in    carboniferous    limestone 

district  in  Derbyshire 

—  congenital 

—  and  drinking-water 

—  in  fowls  on  meat  diet 

—  iodine  in  relation  to 

—  parenchymatous 

—  prevention  bv  iodiferous  rock- 

salt  '. .  . ,        174,  176 

—  reason    of    enlargement    of 

thyroid     ..  ..  ..     175 

—  theory  of  bacterial  origin  . .     177 

—  thymol  in      ..  ..  ..     177 

—  treatment      ..  ..  ..     174 

—  wells  ..     174,  176,  177,  178,  184 


194 

137 


144 
237 


98 
191,  193 
194 
197 
145 
145 
186 


146 
145 
145 
146 

145 
187 
212 
169 
205 


189 
189 


174 


173 

176 

173, 

177 

175 

173, 

175 

173, 

182 

282 


INDEX 


PAGE 

Goitre  in  whelps            . .          . .  168 

GoU,  columns  of . .          ..          ..  213 

Goodman,  transfusion  in  haemo- 
philia       . .          . .          . .  41 

Gower's  tract      ..          ..          ..  213 

Gracile  nucleus  ..          ..          ..  213 

Groves,  Hey.  on  bone  growth  . .  159 

and    Walker    Hall,    on 

colon 132 

Growth  in  relation  to  vitamines  5 
Griinbaum,  oedema  of  lungs  after 

saline  transfusion           . .  104 
Guanidine     intoxication     and 

tetany       . .          . .          . .  170 

Gull  and  Ord  on  myxoedema    . .  166 
Gummata,  iodides,  and  thyroid 

extract     . .          . .    "    178,  180 

Gum-saline  solution  in  shock  . .  101 


HiEMATEMESiS  uithout  ulcer  . .  128 
Haemoglobin  after  haemorrhage  18 
Haemolytic  toxin  in  spleen  . .  27 
Haemophilia         . .  . .  . .       33 

—  antithrombin  not  in  excess  in       38 

—  blood  transfusion  for  . .       20 

—  calcium  salts  for       . .  .  .36,  40 

—  carbon  dioxide  gas  for        . .       40 

—  causes  of  delay  in  coagulation       35 

—  deficiency  of  polymorplis  in       35 

—  delay  in  thrombin  formation  36 
• —  delayed  coagulation  time    . .        34 

—  effect  of  locaUty  and  nature 

of  injury  . . 

—  fibrinogen  in. . 

—  fragility  of  vessel  wall  in    . . 

—  horse-serum  for 

—  magnesium  lactate  for 

—  non-hereditary  cases 

—  normal  human  blood  for    . . 

—  prothrombin  in         . .  36, 

—  relation  of  leucocytes  to     . . 

—  researches  of  Addis  36, 


—  reverse    action    of     calcium 

salts 

—  round-bodied  needle  in 

—  Sahli  on 

—  spontaneous  arrest  of  bleeding 

—  styptics  for    . . 

—  thrombokinase  in     . . 

—  transfusion  for 

—  treatment  of  bleeding 

—  —  causes 

—  Wright's  physiological  styptic 

for 
Haemorrhage,  blood-pressure  after 

—  blood  transfusion  for 

—  blood  volume  after  severe  . . 

—  due  to  food  deficiency 

—  in   haemophilia    (see   Haemo- 

philia) 


36 
35 
40 
40 
34 
39 
37 
37 
37 

40 
39 
36 
34 
39 
36 
41 
39 
38 

39 
17 
19 
18 


40 


PAGE 
Haemorrhage,  jaundice  and        28,  38 

—  nucleated  red  corpuscles  in 

regeneration   after         . .       18 

—  in  pernicious  anaemia  . .       38 

—  purpura  . .  . .  . .        38 

—  recovery  after  . .  . .       16 

proteins  after     . .  . .       18 

—  red  marrow  increased  after      18 

—  restoration    of    blood-serum 

—  proteins  after  . .  . .       18 

—  reticulated  cells  in  blood  after      18 

—  in  scurvy        . .  . .  . .       38 

—  secondary,  in  war    . .  . .       16 

—  and  shock      . .  . .  . .       81 

—  spasm  in  veins  after  . .  17 
Halliburton  and  Drummond,  on 

fat-soluble  A       . .  . .         6 

Eandelsman  on  pituitary  . .     188 

Harrison,  Ross,    on    growth    of 

axon  . .  . .         . .     230 

Edrtel  on  gastrojejunostomy  • .  130 
Hatteria's  functionless  unpaired 

eye  197 

Hay  fever,  foreign  protein  as  a 

cause  of  . .  . .  . .       42 

test  for     . .  . .       43 

Head  on  localization  of  sensation     242 

—  on  peripheral  sensation       .  •     212 

—  spinal  areas  . .  . .  . .     225 

Headache  . .  . .  . .       31 

—  '  lymphatic,'  calcium  salts  for      43 

—  and  pituitary  gland  . .  195 
Hearing,  cerebral  localization  . .  239 
Heart,  the  45 

—  abnormal  ventricular  complex     74 

—  afferent  nen-es  from  . .       62 

—  arrhythmias  of  . .  . .  63 
prognosis  in         . .          . .        78 

—  atrioventricular  rhythm  52,  56,  57 

—  atropine  and  the       . .       . .  61,  68 

—  auricle    and    ventricle    syn- 

chronous . .  . .  . .       52 

—  auricular  fibrillation  52,  75,  79 
flutter 79 

—  auriculo-ventricular  bundle  47,  55 

rate  of  conduction  . .       58 

node         . .  47,  55,  71 

—  in  birds,  conduction  path  . .       48 

—  block  61,  64,  65,  67,  78 
effect  of  atropine  ..       68 

—  blood-vessels  in  shock         . ,       83 

—  complete  irregularity  of     . .       52 

—  complexes     from     abnormal 

beats         . .  . .  . .       54 

—  conduction  path  in  man    . .       47 

—  contractile  power     . .  . .       61 

—  currents  . .  . .  52,  54 

—  depressor   nerve   fibres   and 

blood  pressure    . .  . .       62 

—  development  and  structure         45 


INDEX 


288 


PAGE 

Heart,  different  actions  of  right 

and  left  vajn       •  •  •  •       ^'^ 

—  diaitalis  as  cause  of  fibrillation      47 

—  effect     of     movement     and 

emotions  on        . .  . .        03 
riieumatism  on  . .  64,  76 

—  electrocardiotrrapby  of        . .       52 

—  extrasystoles  of        . .  . .       69 

—  graphic   methods,    necessity        73 
idioventricular  riiythm 

57,  01,  65,  66,  76 

—  irrepiilarities  of         . .  . .  63 

defect  in  conductivity  . .  64 

contractility  . .  . .  77 

increased  excitability    . .  68 

of  nervous  orii^in  . .  63 

—  lesions  of  auriculoventricular 

node  and  bundle            . .  68 

—  and  medulla  . .          . .          . .  60 

—  modes  of  examination          . .  48 

—  miiscle,  properties  of           . .  57 

—  nature   of   stimulus   causing 

contraction          . .  . .  58 

—  nen'ous  system  of  . .  . .  60 

—  pace-makers  of         . .  . .  57 

—  pain  in            . .          . .  . .  63 

—  paroxysmal  tachycardia  . .  74 

—  point  of  origin  of  heart  beat  47 

—  polygraphic  tracings  . .  48 

—  premature  beats      . .  66,  69 

pulsus  altemans  with       78 

sisznificance    . .  . .        72 

—  pulsus  altemans       ..  ..       77 

—  rate  of  beat,  factors  of        . .       62 

—  refractory  period      . .  . .       59 

—  retrograde  beat  in  tachycardia     74 

—  reversed  rhythm       , .  . .       47 

—  rhythms         . .  . .  56,  75 

—  sino-auricular  node  . .  . .       47 

—  sinus  arrhvthmia     . .  63,  78 

—  stand-still"  of  ..  64,  67 

—  sympathetic  fibres,  action  of       62 

—  tachycardia   . .  62,  69,  73,  75 

—  tonicit.v  of     . .  . .  . .        59 

—  vagus  nerve,  action  of         . .       61 

—  ventricular  fibrillation  from 

adrenalin  . .  . .     205 

in  chloroform  poisoning     77 

Hemianaesthesia  . .  . .  . .     243 

Hemianopia        . .  . .        238,  243 

Hemiplegia  209,  226,  243,  249 

Heparin  . .  . .  . .       30 

Heredity 148 

Hernia,  stranqnlated,  and  arrest 

of  peristalsis         ..  ..     117 

Hindhede  on  food  required        . .         2 
Histamine  poisoning  and  shock 

84,  91^  94 
Holmes,    Gordon,    on    cerebellar 

lesions 262 


PAGB 

Holmes,   Oordon,  and  Lister  on 

hemianopia          . .          . .  238 

Hopkins  on  vitamines  . .          . .  6 

'Hormonal'         120 

Hormone,  peristaltic     . .          . .  120 

Honnones  from  ductless  glands  144 
Horse-serum     for    hajmophilic 

bleeding    . .          . .          . .  40 

Horsley  on  pituitary       . .          .  •  188 

—  on  removal  of  cortical  centre  241 

—  and  Clarke  on  the  cerebellum  259 
Hoicland  and  MarrioU  on  blood 

calcium  in  tetany  . .  170 
Hunt,  Ramsay,  on  double  motor 

path  in  nerves  ..  ..  210 
on  nerve  suture  . .          . .  211 

—  and  Seidel    on    activity    of 

thyroid     ..          ..          ••  1"5 

on  iodine  in  thyroid       • .  175 

on  iodoform  and  thyroid  179 

Hunter,     experiment    on    bone 

growth      . .          . .          .  •  15S 

Hunter's  giant     . .          . .          . .  191 

Hurst  on  ileocaecal  sphincter    . .  114 

—  on  sensory  functions  of  viscera  121 
Huriritz  on  blood-serum  proteids  18 
Hydatid  cysts,  risk  of  anaphylaxis 

in  operations  on . .  . .  42 
Hydraemic  plethora  after  saline 

transfusion  . .  . .  104 
Hydrocephalus  . .  . .  256,  265 
Hydrochloric   acid   in   stomach, 

variations  in  ..  ..  123 
Hyperchlorhydria    and    gastric 

ulcer         . .          . .          . .  125 

—  organic  disease          ..          ••  126 

—  pyloric  spasm             . .          •  •  125 

—  relation    to    appendix    and 

gall-bladder         ..  .,126 

—  treatment       . .          . .          . .  128 

Hypernephroma,  effect  of        . .  145 

Hyperpituitism,  results  of        ..  193 

—  treatment  . .  . .  •  •  194 
Hyperthyroidism  in  soldiers  . .  182 
Hypopituitism    (Frohlich  type), 

treatment            . .          .  •  195 

—  results  of 193 

ILEAL  kink           119 

—  stasis  and  gastric  stasis  . .  116 
Ileocaecal     sphincter,     clinical 

observation  of     . .          . .  115 

function  of           . .          . .  114 

gastric  symptoms           ..  127 

incompetence  of             . .  117 

Heosigmoidostomy,  ileal  safety- 
valve  operation  . .        114,  120 

—  discomfort  after  ..  -.  113 
Ileum,  artificial  anus  in,  may  be 

fatal          132 


284 


INDEX 


PAGE 
Impotence  . .  . .        146,  194 

—  and  pituitary  trland. .  . .     192 
Iodine  and  thyroid        174,  175,  178, 

180,  182 
Iodoform  poisoning  and  tyhroid- 

ism  ..  ..  ..     178 

lodothyrin  ..  172,  175,  181 

Infantile  palsy    ..  ..  ..     217 

Infantilism  and  pituitary  gland 

192,  193 
Infants,  two  forms  of  dyspepsia  in     126 
Infections,  acute,  and  shock    . . 
Internal  capsule,  lesions  of 
Intestinal  colic,  cause  of 

—  paralysis  toxjemia  in  shock 
■ treatment  of       . 

—  shock 

—  stasis,   hypochlorhydria   and 
Intestines,  antiperistalsis  in     . . 

—  mimicry  of  chronic  stasis    . . 

—  constipation  and 

—  isolated    loop    causes    fatal 

toxaemia  . . 

—  Jackson's  pericolic  membrane 

—  Lane's     chronic     intestinal 

stasis  in    . . 
movements  of 

—  nervous  mechanism  of 

—  and  nervous  reflexes 

—  peristalsis  of 

—  toxins  in  stasis 
Intoxication  hydatique 


81 
210 
118 

81 
118,  196 

11 
127 
112 
119 
118 

120 
119 

119 
111 
111 
119 
111 
120 
42 


JaCKSOK'S  pericolic  membrane  119 
Javmdice,  calcium  chloride  before 

operations  in       . .          . .  38 

—  coagulation  time  in. .          . .  38 

—  haemorrhage  in          . .          . .  38 

—  risk  of  operations  in            . .  38 
Jaw,  shape  of     . .          . .          . .  1-56 

Johnson  on  hyperthyroidism    . .  182 

Keith's  '  vital  red '   method  of 

estimating  blood  volume  17 

—  on  blood-volume  in  shock    86,  87 

—  on  sphincters  of  gastro-iutes- 

tinal  tube  . .  . .  114 
KendaU,   indol   derivative  from 

thyroid 173 

Kerr  on  blood-serum  proteids  . .  18 

Kidney  hypertrophy,  reason  of  176 

—  movable,  and  gastric  sym- 

ptoms       . .          . .          . .  127 

Kinsesthetic  sense           . .          . .  212 

Knee-jerks  in  shock       . .          . .  82 

Kocher    on    parathyroids     and 

tetany       . .          . .          . .  183 

Kohn  on  parathjToids    . .          . .  169 

Kropfbrunnen  or  goitre  wells 

174,  176,  177 


PAGB 

Labour  pains,  caution  necessary 
in  using  pituitary  extract 

for             196 

Labyrinth  and  nystagmus        . .  262 

—  vertigo            262 

Lactation,  foetal  internal  secre- 
tion and         . .                . .  147 

—  belladonna,  pilocarpine    and  147 

—  pituitary  extract  and  147, 190, 196 

—  recent  increase  of               . .  146 

—  in  Siamese  twins     . .          . .  147 

—  'witch's  milk  ..  ..  147 
Laidlaw    and   Ryffel,    on   rectal 

feeding      . .          . .          . .  132 

Lane's  chronic  intestinal  stasis  119 

Langley  on  nerve  anastomoses. .  234 

Lard,  absence  of  fat-soluble  A  in  6 

Lasesne's  sign     . .          . .          . .  220 

Lassitude  due  to  food  deficiency  7 

Lee  and  Minot  on  blood  platelets  32 
Left-handed  persons,  proportion 

of.  in  community            . .  250 

Lemon-juice  and  scurvy           . .  8 

Lenticular  nucleus          . .          . .  210 

Leriche  and  Policarde  on  cartilage 

grafts        . .          . .          . .  165 

Leucocytes  and  chemical  attrac- 
tion             231 

—  in  haemophilia  . .  35,  37 
Levy  on  adrenalin  and  the  heart  205 

—  on   chloroform  poisoning    . .  202 
Liepman  on  apraxia      . .         248,  249 
Lime  juice  and  scurvy  . .          . .  8 

Lissauer"s  tract  . .          . .          . .  212 

Liver  and  antithrombin  forma- 
tion             30 

—  blood-destroying  functions  of  28 

—  not  engorged  in  shock          . .  84 

—  and  restoration  of  blood  pro- 

teins after  haemorrhage. .  19 
Lumbar   piancture,    aid   in    dia- 
gnosis       . .          . .          . .  265 

Lungs,   (Oedema  of,   after  saline 

transfusion           . .          . .  104 

Macallum  on  tetany      . .          . .  183 

McCarrison  on  endemic  eroitre. .  177 

—  effect    of    rice    on  adrenals, 

testes,  ovaries,  and  spleen  5 
Macewen  on  bone  growth  153, 

155,  161 
Magnesium  lactate  in  haBmophilic 

bleeding   . .          . .          . .  40 

—  salts    more    effectual    than 

calcium     . ,          . .          . .  44 

M'alnutrition  and  tetany  . .  170 
Margarine  content  of  fat-soluble  A  6 
Marie  on  aphasia  . .  251,  252 
Marine  on  prevention  of  goitre 

in  lambs  and  do^          . .  174 


INDEX 


285 


PAG£ 

Harrow    chances    after    splen- 
ectomy     . .  . .  . .       27 

Mtnhall  and  Heapt  on  menstrua- 
tion in  animals       . .  . .     138 

Iffeat,  antineuritic  substance  in  5 

—  fresh,  as  antiscorbutic  8,  10 

amount  of  vitamine  in . .         9 

Median    nerve,    recovery    time 

after  injury         . .  . .     232 

Mecakaryocytes  and  platelets..       32 
Ueilanby  on  rickets      ..  12,  13 

Meninffitis  . .  . .         256,  257 

—  and  cardiac  arrtjythmia 

—  lumbar  puncture  in . . 

—  septic,  atropine  in  . . 
Menopause,  artificial,  and  ovarian 

feeding 

—  and  calcium  salts    . .  44,  142 
Menstrual  headache  and  pituitary 

extract 
Menstruation 

—  painful 

—  precocious 
Mental   lethargy  in  bypopitui- 

tism  . . 

Menthol  as  local  analgesic 
Metabolism  in  shock. . 
Microcytes,  source  of    . . 
Milk   (see  also  Lactation) 

—  antineuritic  substance  in   . . 

—  as  an  antiscorbutic  . . 

—  as  a   cause   of  asthma   and 

hay  fever. . 

—  clotting  in  stomach,  reason 

for  

—  efifect  on  rickets 
teeth         

—  fat-soluble  A  in 

—  long  pancreatized  as  nutrient 

enema 

—  secretion  of  . . 
Mitosis 

Moore  on  alkalosis  in  shock 
Moratcski  on  pituitary  . . 
Morphia  in  shock 
Moss  on  blood  groups  . , 
Motor  path,  the  double . . 
MoU  on  nerve  cells  in  shock  . . 
MoU  and  Hailiburton  on  nerve 

regeneration 
Mould,    poisonous,   in   atropine 

solutions 
Motissu  on  parathyroids 
Murray  on  thyroid  feeding     . . 
Muscle  end-plates 

—  heart  and  skeletal  compared 

—  refractory  period 

—  striped,  structure  and  function  211 

—  submaiimal  contractions   . .       59 
—  tone 59,  210 


63 
265 
265 


141        — 


195 
137 
146 
145 

194 
27U 

87 


11 

43 

109 
13 

13 
6 

273 
146 

148 
88 

183 
99 
23 

208 
88 

229 

204 
169 
166 
210 
59 
59 


PAGE 
Muscle    tone,    loss  of.    in   poet- 
central  injury     . .  . .     245 

in  posterior  nerve-root 

injury  ..  ..225 

in  shock         . .  95,  96 

and     vestibular     nerve 

nuclei   ..  ..  95,  98 

—  unstriped,    and    pituitary 

extract     . .  190,  196 

Musculospiral     nerve     injury, 

recovery  time     . . 

spontaneous  recovery 

Music,  effect  of,  in  brain  injury 

Myelitis,  transverse 

Myositis    o^ificans,    traumatic, 

cause  and  treatment  of . . 

universal,  cause  of 
Myxoedema  . .  . .        166, 

—  arteriosclerosis 

—  in  monkeys    . . 

—  tetanv      and 


—  and  thyroid  grafting 

—  treatment 

Nerve,  anastomosis  of . . 

—  ceUs  in  shock  . .  88 

—  diagnosis  of  injury  to 

—  effects  of  notching  . . 

—  injury,    chemical    attraction 

of  new  fibre  in    . . 

electrical  tests  of  limited 

value    . . 

end-to-end  suture  for  . . 

Forssman's    experiments 

incomplete  section 

medullary  degeneration 

—  —  operation  for,  by  anasto- 

mosis   . . 

—  bridging 

Cargile  membrane   . . 

—  — -  —  choice  of 
devices    for    approxi- 
mating divided  ends 

by  grafting   . .        233, 

—  splitting 

— ■ tendon  transplanting 

— transplantation        233, 

reaction  of  degeneration 

not  always  reliable    . . 

prognosis 

— -  —  recovery  time  after     231, 

regeneration  after 

repair  of  . . 

secondary  suture,  causes 

of  failure 

—  —  spontaneous  recovery  from 

—  — ■  time  for  operation       228, 

—  —  Tinel's  test 

Trotter's  phenomenon  . . 

war  experience  of 


232 
228 
243 
216 

160 
161 
171 
180 
168 
167 
183 
173 

235 
,  93 
227 
235 

230 

227 
235 
231 
233 
230 

234 
233 
234 
233 

236 
235 
233 
236 
235 

227 
332 

232 
229 
227 

231 
227 
231 
228 
233 
235 


286 


INDEX 


PAGE 

Nerve  roots,  posterior,  function  of  209 

section  of      . .         213,  225 

structure  of  , .          . .  212 

surgery  of      . .          . .  226 

—  supply  of  flexors  and  extensors  217 

—  peripheral,     non-medullated 

fibres  in    . .          . .          . .  211 

—  sensory,  overlapping  of       . .  216 

—  spinal,  segmental  distribution 

216,  218 
Nervous  diseases  and  arrest  of 

peristalsis             . .          . .  117 

—  instability  in  soldiers           . .  182 

—  system,  central,  regeneration 

of 224 

Neurasthenia,  traumatic           . .  221 

Neuritis  and  beri-beri    . .          . .  3 

Neuroses  and  arrest  of  peristalsis  117 
Nitrogen  absorption  from  amino- 

acids          ..          ..          ..  273 

—  increased     excretion    after 

amino-acid  feeding             • .  274 

—  output  after  nutrient  enemata  275 
Notthajt  on  exophthalmos  . .  172 
Novocain   for   anoci-association 

anaesthesia  . .  . .  103 
Nutrient  enema,  useful  form  of 

134,  136 
Nystagmus  in  cerebellar  lesions 

261,  263 

—  differential  diagnosis  of  cause  262 

Obesity,  blood  volume  in  . .  18 
CEsophagus,     temperature    and 

tactile  sense  in    . .          . .  121 

Oophorectomy,  effects  of  . .  140 
Operations,  prevention  of  shock 

in 102 

Opium,  effect  of,  on  skin         . .  270 

Optic  atrophy  from  iodoform  . .  179 

—  neuritis           . .          . .          . .  257 

— ■  thalamus,  function  of         . .  243 

Oranses  as  antiscorbutics  . .  10 
Osteoblasts          ..           152,  154,  155 

—  embolism  from  . .  . .  161 
Osteomalacia  and  parathyroids  170 

—  treatment  by  adrenalin       . .  146 

—  and  ovary      . .          . .          . .  141 

Osicald  on  iodine  in  thyroid   175,  176 

—  on  iodothyrin  . .  172,  175 
Ovary  affected  by  polished  rice 

diet           . .          . .          . .  5 

—  effect  of  calcium  salts  on    . .  43 

—  functions  and  structure       . .  137 

—  graft  of           140 

—  internal  secretion  of  138, 

140,  141,  145 

—  internal  secretion,   effect   of 

excessive              . .          . .  145 
on  mammary  cancer  140 


Ovary,  internal  secretion, 
on  vascular  system 

—  and  lactation 

—  menstruation 

—  before  puberty 

—  and  osteomalacia 
Ovulation 

Ovum,  development  of. . 

—  and  heredity 
Oxalate  calculi    . . 
Oxalates,  metabolism  of 

—  from  carbohydrates.. 

—  sources  of 
Oxaluria  . . 

—  treatment  of 
Oxygen  famine  in  shock 


effect 


PAGB 

140 
147 
137 
145 
141 
138 
147 
148 
200 
198 
199 
198 
198 
200 
98 


Pacchionian  bodies     . .        . .    265 
Pain,  localization  of       . .  . .     243 

—  in  nerve  injury  . .  . .     229 

—  section  of  pain-fibres  in  cord 

for  220 

posterior  nerve-roots  for    226 

Paralysis,  bilateral  spastic       . .     216 

—  of  cranial  nerves      . .         255,  263 

—  flaccid  247 

—  functional,  from  division  of 

posterior  nerve-roots     . .     225 

—  infantile,  nerve  anastomosis  in  235 

—  spastic  . .  .  •  . .     256 
Paraplegia,    spastic,    section    of 

posterior  nerve-roots  for 
Parasyphilis  of  central  nervous 

system 
Parathyroid  glands 

effect  of  calcium  salts  on 

—  removal  of     . 

and  osteomalacia 

secretion  of 

and  tetany 

Pardee  on  pituitary 
Pastures,  difference  in  . . 
Paton,  Noel,  on  tetany  . . 
Paulesco  on  pituitary     . . 
Pearce    on    spleen    and    blood 

corpuscles 
Peas,  germinating,  antiscorbutic 

vitamines  in 
Pelvirectal  sphincter 
Periosteum  (see  also  Bone  Growth) 

—  Macewen's  views  on  role  of 

—  preservation  in  operations . . 
Peristalsis,  arrest  of,  causes  and 

treatment 

—  pituitary  extract      . .         118,  196 
Periostitis  and  formation  of  new 

bone         . .  . .  . .     161 

Pernicious  anjemia,  blood  trans- 
fusion for  . .  . .       20 

Perroncito  on  nerve  regeneration    229 


226 

265 

166 

43 

169,  183 
.,  170 
..     183 

170,  183 
..     196 

7 
..     170 
188 

26 

10 
114 

156 
163 

117 


INDEX 


287 


PAGB 

Physostipmine     in     arrest     of 

peristalsis  . .  . .     117 

Piceons,  neuritis  in       . .  . .         4 

Pike  on  spinal  shock  and  blood- 
pressure    . .  . .  . .       96 

Pilocarpine  and  milk  secretion       147 
Pineal  glands      . .  . .        145,  197 

Pituitary  extract  for  intestinal 

paralysis  . .  100,  118,  196 

for  labour-pains,  caution     196 

and    lactation      147,  190,  196 

in  shock    . .  . .  . .     196 

and  unstriped  muscle  190,  196 

usage  and  dosage  190,  195,  196 

—  feeding  causes  emaciation  . .     190 

for  delayed  puberty       . .     145 

harmful  in  acromegaly..     194 

and  headache      . .  . .     195 

—  gland  and  acromegaly      191,  193 

and  adiposity     . .  . .     192 

anatomy  of         . .  . .     186 

and  bone  growth         156,  165 

and  blood-pressure        . .     190 

clinical  results  of  lesions  of    191 

—  —  connection  with  thyroid       190 
effects  of  removal  of  145, 

187,  192 

functions  of        ..  ..     193 

gigantism  191,  193,19-4 

in     hyperpituitism     and 

hypopituitism  . .     193 

and  infantilism    189,  192,  193 

and  malignant  growths       194 

relation  to  sterility  and 

impotence        . .  . .     146 

and  sugar  metabolism 

189,  192,  194 

—  tumour  and  blindness      192,  194 

x-ray  diagnosis  of         . .     192 

Pleasure,   localization  of  sensa- 
tion of 243 

Poikilocytes,  source  of..  ..       25 

Pollen  a  cause  of  asthma  and 

hay  fever  . .  . .       43 

Potassium  citrate  and  oxaluria     200 

in  shock  . .  . .  . .       99 

Potatoes  as  antiscorbutic        . .       10 
Pott's    disease,    Albee's    bone- 
grafting   for        . .  . .     163 
Phloroglucin   and  vanillin   test 

for  HCl 123 

Precocity,  pineal  tumour  and..     197 
Pregnancy  after  bilateral  ovari- 
otomy        139 

—  blood-volume  in       . ,         . .       lb 

—  chemical  diagnosis  , .  . .     151 

—  and  coagulation  time  of  blood       30 
Proantithrombin            . .          . .       30 
Prostate,  atrophy  after  castra- 
tion   143 


PAGE 

Protein  in  diet  . .          . .          . .  2 

—  foreign,  cause  of  asthma  and 

hay  fever             . .          . .  42 

—  placental,    serum    diagnosis 

of  pregnancy  from         . .  151 

—  in  stomach  . ,  . .  . .  109 
Prothrombin       . .          . .          . .  29 

—  in  haemophilia  . .  36,  37 
Protopathic  sense  ..  ..  212 
Puberty,  delayed  and  pjecocious  145 
Pugilist's  '  knock-out  blow  '  on 

chin           98 

Pulse  tracings     . .          . .          . .  48 

Pupil,  dilating  fibres  of            . .  217 

Purpura 28,  38 

—  hjemorrhagica  . .  . .  32 
Pylorus,  action  of           . .          . .  108 

—  congenital  stenosis  of         • .  126 

—  spasm    of,    and   hvperchlor- 

hydria      . .       '  . .          . .  125 

—  sphincter        ..          ..          ..  114 

Pyramidal  tract              . .          . .  208 

and  muscle  tone             . .  210 

Pyrosis     . .          . .          . .          . .  125 

Ql1NrS"E-UREA-HYDR0CHT/0RroE 
for  anoci-association  ames- 

thesia 103 

Ranke,  diet  tables          . .          . .  3 

Ransom  on  sensory  paths  in  cord  212 

—  and  Laycock  on  sensation  . .  241 
Ranaom'.^  silver-pyridine  method  210 
Rectal  feeding     . .          . .          . .  132 

Rectum,  absorptive  power  of . .  132 
Red     marrow     increased     after 

haemorrhage        . .          . .  18 

Red  nucleus       . .         . .         . .  210 

Renal  calculi  mostly  oxalate  . .  200 
Reticulated  cells  after  haemorrhage    18 

Retina,  representation  in  cortex  238 

Rhubarb  and  oxaluria  . .          . .  198 

Rice  and  beri-beri          . .          . .  4 

Rice-husk  extract  as  antineuritic  5 

Rickets 11 

Ri'ldoch  on  injury  of  spinal  cord  223 
Right-handed     people,     brain 

localization          . .          • .  250 

Rigidity 247 

—  decerebrate   . .             95,  209,  210 
Ringer's  fluid      . .          . .          . .  104 

Roger  on  nerve-cell  inhibition  or 

fatigue  in  shock  . .  93 
Rogers,  hypertonic  saline  solution 

in  cholera            . .          . .  103 

Romney,  difference  in  pastures  at  7 

Roos  on  activity  of  thjrroid     . .  175 

—  on  thyroid  feeding  . .  172 
Rous  and  Turner,  on  preserved 

red  corpuscles     . .         . .  21 


288 


INDEX 


PAGE 
36 
99 

103 
169 


PAGE 


Sahli  on  haemophilia     . . 
Saline,  rectal,  in  shock. . 

—  solution  in  cholera  (Rogers) 
Sandstrom  on  parathyroids 
Sarcoma   cells,   action   of   vita- 
mines  on . . 

ScTiafer  on  pituitary  gland      . . 
Sciatic  nerve,  section  of,  effect 

on  vessels 
Scopolamine  in  general  anaesthesia  204 
Scurvy      . .  . .  . .  • •         7 

—  haemorrhage  in         . .  . .  ^    38 

—  infantile         . .  • .  ",  11 
Sea-urchins,  ovum  development 

in  . . 
Sensation  in  alimentary  canal. . 

—  peripheral 
Sense,  epicritic   . . 

—  muscle,    joint,    and    tactUe, 

path  of    . .  . .         214,  216 

—  pam    . .  . .  •  •         -'-"»  --■'■ 
and  temperature,  path  of 

214,  216 


195 

84 


149 
121 

212 
212 


21: 
212 
212 
42 
149 
145 
132 


—  protopathic    . . 
Sensibility,  deep 
Sensory  path,  double 
Serum  sickness  . . 
Sex,  causation  of 
Sexual  precosity 
Sharkei/  on  rectal  feeding 
Sfierreii  on  appendix  in  duodenal 

and  gastric  ulcers 

—  on  time   relations   in   nerve 

injuries     . . 
Sherrington  on  motor  reflex  arc 

—  on  pain  impulses 

—  on  pain-path 

—  on  postcentral  cortex 

—  on  spinal  areas 
shock 

—  on  transection  of  cord 

—  and    Leyton     on    Broca's 

convolution 

recent  brain  localization 

on  '  silent  area  ' 

Schi^  on  thyroid 

Shock    (see    also    under    intra 

venous  transfusion) 

—  after  abdominal  injury  82,  86 

—  abdominal  vessels  not  dilated      84 

—  acapnia  theory  of    . . 

—  acidosis  in     . . 

—  adrenalin  dangerous  in 

—  alcohol  harmful  in  . . 

—  alkaline    and    saline    trans- 

fusions in 

—  arteries  contracted  in 

—  blood-count  in  85,  S 

—  blood-pressure  in 

—  blood  stagnation  in 


126 

231 
209 
214 
220 
241 
225 
95 
221 

252 
246 
248 
166 

80 


92 

87 
100 
100 

88 

83 

87,  94 

94,  96 

.   86 


Shock,  blood  volume  in   . . 

—  capillaries  in 

—  changes    in    cells    of    liver, 

adrenals,  and  brain  (Crile) 
nerve  cells 

—  chemical     poisoning     (auto- 

lysis) theory  of  . . 

—  (Mle's  method  of  prevention 

—  crush-products  as  a  cause  of 

—  diagnosis  of  . . 

—  experimental 

—  heart  and  blood-vessels  in 

—  and  histamine  poisoning 

—  '  intestinal '   , . 

—  intravenous    saline    trans- 

fusion for 

—  knee-jerks  in 

—  metabolLsm  in 

—  morfihia  in     . 

—  phenomena  of 
pituitary  extract  in 


84 
93 


90 

102 

89 

81 

89 

.   83 

91,  94 

.  117 

.  103 

.   82 

.   87 

99 

.   82 

100,  196 

pre'^ention  and  treatment  of       98 

—  prognosis  from  blood-volume 

and  blood-pressure  . .  86 
saline  per  rectum  in  . .  106 

—  spinal              .  .           .  .  94,  221 

—  spasmodic      contraction  of 

superficial  veins  in         . .       83 

—  strychnine   useless,    possibly 

dangerous,  in      . .          . .  100 

—  theories  of     . .          . .          . .  91 

—  treatment,  blood-transfusion  102 

camphor  . .          . .          . .  100 

fluids        98 

digitalin 100 

gum  and  dextrose  solution 

(Erlanger  and  Gasser)  101 
gum-saline  solution  (Bay- 

liss) 101 

potassium  citrate           . .  99 

saline  by  rectum            . .  99 

transfusion    . .          . .  101 

sleep         99 

tea  or  coffee        . .          . .  99 

warmth    . .          . .          .  •  99 

Short,  Rendle    on    absorption  of 

aminoacids  by  rectum  . .  133 

—  on    absorption    of    nitrogen 

from    amino-acids.  273 

—  on  blood-count  in  shock     . .       86 

—  on  blood  pressure    . .  . .     225 

—  on  blood  C0„   in  shock      , .        92 

—  on  blood-volume  in  shock    85,  86 

—  on  chronic  thyroid  intoxica- 

tion and  iodoform          ,.  179 

—  on  nerve  cells  in  shock        . .  88 

—  on  nerve  injuries       . .          . .  235 

—  on  oxaluria   . .          . .          .  •  198 

—  on  rectal  feeding      . .          . .  133 

—  on  suprarenal  theory  of  shock  92 


INDEX 


289 


PAGE 
181 
97 


Shctrt,  Rendle,  on  svphilitic  ulcers 

—  tlieorj-  of  sliock 

—  treatment  of  intestinal  par- 

alysis 

—  on  wound  of  frontal  lobe 

—  and  Salisbury  on  cutaneous 

ansEsthetics 
Sinus  arrhythmia 
Sinu-auricuhir  node 
Skin,  unbroken,  and  local  anses 

thetics 
Sleep  in  shock    . . 
Smell  a  chemical  aialysis 
Smith,  Miff  A.  //.,  on  value  of 

lime-juice 
Sorrel  and  oxalates 
Souttar  on  gastric  crises  of  tabes 
Space,  recognition  of     . . 
Spasticity 
Spermatozoon,  chemical  action 

—  division  of     . . 
Sphincters    of    pastro-intestinal 

tube  (Keith) 
Spinal  cord,  complete  transec 

tion,  effects  of    . . 
Spinal  cord,  concussion  of  81,  221,  222 

degenerative  changes  after 

division  of  posterior  nerve- 
roots  . . 

functions  of 

injuries,  diagnosis  of     . 

operation  for 

sensory  paths 

tumours,  effects  of 

—  shock 

Spinothalmic  tracts 
Spleen  affected  by  polished  rice 

diet  

—  and  blood 

corpuscles 

diseases    . . 

—  haemolytic  toxin  in  spleno- 

megaly 
Splenectomy   in   dogs,    changes 
after 

—  in  man 

Splenic  vein,  diversion  into  in- 
ferior vena  cava  as  sub- 
substitute  for  splenectomy 

Splenomegaly 

Squint,  convergent,  due  to  dis- 
placement of  brain 

Starfish,  development  of  ovum  of 

Starling  and  Lane-Claypon  on 
lactation  . . 

Starr  on  tumours  of  cerebello- 
pontine angle 

Starvation,  carbohydrate 

—  fat 

—  protein 


118 
247 

267 
63,  64 
63 

267 

99 

231 

9 
198 
220 
244 
209 
of  149 
148 

114 


226 
. .  208 
. .  221 
..     223 

212 
'. '.  214 
94,  221 
. .     213 


27 


255 
149 


14? 


263 
1 
2 
2 


92 
64 
125 
126 
170 
121 
126 
109 
109 
108 
128 


PAGE 
Starvation,  survival  in  . .     1 35 

Sterility   ..  142,  143,  146,  194 

StereocmosLs  212,  213,  214,  233 

Sleicart  and  Rogoff  on  suprarenal 

theory  of  shock  . . 
Stokes-Adams  syndrome 
Stomach,  antipepsin  in 

—  congenital  pyloric  stenosis 

—  dilatation  and  tetany 

—  distention  of 

—  dyspepsia  in  infants 

—  effect  on,  of  tickling  ribs 

—  fast  and  slow  types . . 

—  form  of,  in  life 

—  hemorrhage  without  ulcer 

—  and  'hunger-pain'  124,  126 

—  hunger  sensation      . .  . .     122 

—  hyperchlorhydria      . .        124,  125 

and  on^anic  disease       ..     126 

treatment  of       . .  . .     128 

—  and    intestines,    absence    of 

temperature   and   tactile 

sense  in    . . 

functions  of 

pain  in     . . 

the  seven  sphincters  of 

—  movements  of 

delay  in   . . 

effect  of  character  of  food 

methods  of  observation  of 

—  peristalsis  of . . 
recorded  by  balloon 

—  post-mortem  digestion  of  . . 

—  reflex  flow  of  gastric  juice 

after  nutrient  enema     . . 

—  self-digestion  of 

—  self-regulating  mechanism  of 

acidity 

—  stasis  in         . .  109,  116,  119 

—  symptoms    associated    with 

disease  of  appendix,  gall- 
bladder, etc. 

—  time  of  emptying  and  total 

acidity     in     relation     to 
various  foods 

—  total  acidity . . 

—  variations     in    hydrochloric 

acid 

—  r-ray  examination  of 
Strawberries  and  oxalates 
Strychnine  in  shock 
Styptics  in  haemophilic  bleeding 
Sugar  metabolism  and  pituitary 

gland 
Suprarenal  gland,  enlargement 

effect  of  polished  rice  diet 

Swedes  as  an  antiscorbutic     . . 
Sympathetic  ganglion,  superior 

cervicaC  stimulation    of, 

causes  glycosuria 


121 
107 
121 
114 
107 
111 
109 
107 
108 
122 
125 

135 
124 

123 


127 


109 
123 

123 

107 

198 

100 

39 

194 

145 

5 

10 


189 


290 


INDEX 


PAGE 
Syphilitic  ulcers,  thyroid  feeding 

for            181 

Syringomyelia    ..          ..        214,  216 

Tabes,    gastric   crises,    division 

of  fibres  in  cord  for        . .  220 

—  ' posterior    nerve-roots  226 

Takaki  on  beri-beri        . .          . .  4 

Tannin  in  haemophilic  bleeding  39 

Tea  in  shock       . .          . .          • .  99 
Teeth,  effect  of  fat,  milk,  and 

cod-liver  oil  on                 . .  13 

—  loose,  due  to  food  deficiency  7 
Temperature     of     body     and 

pituitary  gland  . .          . .  192 

variation  on  two  sides. .  248 

Testicular  extract          . .          . .  144 
Testis  affected  by  polished  rice  diet     5 

—  cells  of  Leydig          . .          . .  142 

—  crvptorchism             . .          . .  142 

—  effect     of    ligature    of    vas 

deferens    . .          . .          •  •  143 
castration  in  men  and  boys  142 


eunuchism 

—  functions  of  . . 

—  grafting  in  fowls 

—  internal  secretion     . . 

—  before  puberty 

—  and  spennatozoa 
Tetany,  calcium  chloride  treat- 
ment 

metabolism 

salts  and 


170,  182, 


143 
142 
143 
142 

145 
142 

170 

170,  171 

44,  183 


18; 
170 
170 
170 
170 
183 


cause  of 

—  and  colitis 

—  dilatation  of  stomach 

—  a  guanidine  intoxication 

—  and  malnutrition     . . 

—  milk  for 

—  and  parathyroids     . .        170,  183 

—  in  relation  to  thyroidectomy 

and  myxcedema 
Thiele  on  motor  reflex  arc 

—  on  spinal  shock 
Thiosinamine,  action  of.. 
Thrombin  formation  delayed  in 

haemophilia 


167 

209 

95 

31 


Thrombogen 
Thrombokinase  . . 

—  in  haemophilia  . .  3 
Thrombosis 

Thymus    affected    by    polished 

rice  diet  . . 
Thyroid  colloid,  chemistry  of  . . 

—  feeding 

for  delayed  puberty 

in  myxcedema  and  tetany 

in  normal  subjects 

for    tertiary     syphilitic 

ulcers   . . 


36 
29 
29 
6,  39 

28 


172 
171 
145 
168 
171 

181 


PAGE 
Thyroid    feeding    for  ununited 

fractures  . .          . .          . .  165 

—  gland  (see  also  Goitre) 

active  principle  of          . .  173 

and  bone  growth           . .  165 

in  child 172 

and  cretinism     . .          . .  165 

and  drinking-water       . .  182 

effects  of  deficient  secre- 
tion         146 

effect  of  pregnancy  on..  146 

and  exophthalmic  goitre  181 

and    iodoform  poisoning  179 

iodme  and           . .        180,  182 

iodothyrin  in      . .          . .  181 

operations  on     . .          . .  182 

removal  of           . .         . .  145 

tumours   . .          . .          . ,  173 

—  and  parathyroid  glands       . .  166 

effects  of  removal   . .  167 

grafting          . .          . .  183 

—  swelling  in  trout     . .          . .  174 
Thyroidectomy  in  animals       . .  171 

—  atheroma  after         . .          . .  180 

—  effect  on  pituitary  gland   . .  190 

in  dogs  and  monkeys  168 

changes  in  remnant      . .  169 

—  results  of       . .          . .          . .  171 

Thyroidism        and        iodoform 

poisoning             . .          . .  178 

Tinel's  test          228 

Topfer's    test   for    hydrochloric 

acid  ..  ..  ..123 

Toxaemia,  intestinal,  from  stasis 

81,  120,  121 

—  intestinal  paralysis  in  shock  81 
Transfusion     (see    also    Blood- 
transfusion) 

—  Bayliss's  gum-saline           . .  101 

—  gum   and   dextrose   solution  101 

—  intravenous  saline   . .        101,  103 

Ringer's  fluid           . .  104 

Transverse  colic  sphincter       . .  114 

Tremor  m  cerebellar  lesions   261,  263 

Trephinmg,  palliative   . .          . .  259 
Trophic    lesions    and    posterior 

nerve-roots          . .          . .  225 

Trotter  on  nerve  section  pheno- 
menon     . .          . .          . .  233 

Trout,  thyroid  swelling  in  4,  17 

Tumours  of  brain,  diagnosis 

255,  257,  262,  263 

Turck  on  shock  . .          . .          . .  87 

Twins,     hereditary     tendency 

towards    . .          . .          . .  139 

—  identical  and  ordinary        . .  149 

—  Siamese,  lactation  in          . .  147 

Ulnar    nerve,    recovery    time 

after  injury         . .         . .  232 


INDEX 


291 


Urine,  ammoniacal  fermentation 
and  formation  of  oxalates 

Urotropino  and  cerebros])inal 
fluid  

Urticaria,  deficient  coagulability 
of  blood  . . 

—  calcium  salts  in 


PACiK 
199 


265 


31 
43 


234 
143 


169 


10 


Vagus  nerve  and  glycosuria    . .     189 

and  chloroform  poisoning     202 

— •  —  and    partial    heart-block       G8 
—  and     symjiathetic     nerves, 

experimental  anastomosis 
Yas  deferens,  result  of  ligature  of 
Vassali  and  Generali,  on  para- 
thyroids  . . 
Vegetables,  canned,  absence  of 
antiscorbutic     vitamine 
from 
Veins,  spasm  in,  after  hfemor- 

rhacre        . .  . .  17,  83 

Venous  puLse,  record  of  . .       48 

Ventricular  fibrillation,  in  chloro- 
form poisoning   . .  . .     203 

Vertigo  in  cerebellar  lesions    262,  2G3 
Vestibular     nerve     nuclei     and 

muscle  tone        . .  95,  98 

Vestibulospinal  tract     . .  . .     210 

Vi7icent,  Swale,  on  parathyroids       170 
Visceroptosis       . .  . .  . .     119 

Visuopsychic  area  . .        237,  239 

Visuosensory  cortex       . .         237,  239 
'  Vital  red  '  method  for  estima- 
tion of  blood-volume       17,  86 
Vitamines  . .  . .  . .         6 

—  and  beri-beri  . .  . .    5,  6 

—  in  cabbage,  swedes,  potatoes       10 

—  in  fresh  meat  . .  . .    8,  9 

—  in  germinating  peas  and  beans     10 

—  in  fruit  juices  ..  ..  8-11 

—  in  milk  and  fats      . .  11-14 

—  and  rickets    . .  . .  . .       14 

—  and  scurvy    . .         . .         . .  8-1 1 


PAQR 

War  oedemn,  cause  of  . .          . .  5 

Wasps,  i):irtliogeiiesis  in            . .  148 

Water,  distilled,  bacteria  in  . .  103 
Walson,   Cfialiners,  on  goitre  in 

fowl           175 

Weed  on  motor  reflex  arc          . .  209 

—  dishing, \  and  Jacobson,  on 

pituitary  and  glycogen..  189 
Weight,  power  of  judging,  lost 

in     post-central    cortical 

lesions      . .          . .          . .  244 

Weil   recommends   horse-serum 

for   haimophilic   bleeding  40 

Wei.isman  on  heredity  . .          . .  148 

Wells  on  iodine  in  thyroid        . .  172 

Wiieat,  antineuritic  substance  in  5 

Whelps,  goitre  in           . .          . .  176 

Whipple  on  blood-serum  proteids  18 

White  on  causes  of  eczema     . .  43 

Wilms  on  goitre  wells  . .  . .  177 
Wiltshire    on    lemon-juice    and 

germinated  beans           . .  10 

Windle,  cases  of  pulsus  altemans  78 

'  Witch's  milk  ' 147 

Word    centres,     auditory    and 

visual       . .          . .          . .  251 

Wright    on   carbon   dioxide   for 

hajmophilic  bleeding      . .  40 

—  on  hsemophilia  . .  . .  34 
— •  on  physiological  styptic     . .  39 

Xerophthalma     from     fat- 
starvation            . .          . .  3 

X-ray  evidence  of  course  of  food 

after     gastrojejunostomy  129 

—  picture     of     movements     of 

small  and  large  intestine  115 
of  sella  turcica  in  pituitary 

tumour     . .          . .          . .  192 

urinary  calculi               . .  200 

YEAST,    antineuritic    substance 


3449- 19 


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